Nearly everything in the basement that moves (and a lot of things that don't) is trying to finish what Isaac's mom started. These guys try harder than most.
- The entire class of spider enemies are this both literally and figuratively. They all have erratic movements over random vectors, making it very likely they will collide into you for damage. Even the smaller spiders are dangerous because of this! The Baby Long Legs and Small Baby Long Legs are subclasses of Mook Maker spiders that will actively run away from you while spawning regular spiders (Baby Long Legs) or spider-spawning sacs (Small Baby Long Legs). Failure to kill these enemies quickly will result in the room filling with spiders, very dangerous in the early game when your damage output and tear firing rate are low.
- Special mention goes to Trites. These jumping spiders are just like Hoppers, except they move at nearly double speed, take more hits, and often come in packs of four or more. Most importantly, they can jump about twice as far as Hoppers, and occasionally decide to jump a tile or two behind the player, which makes them impossible to dodge no matter what you do. The expansions even gave them a couple of variants: Raglings spit two orbiting bullets around themselves in addition to jumping and are tougher, but fortunately aren't as aggressive. Blisters spit the same homing Dark Balls spawned by Little Horn, giving you a lot more stuff to dodge; to top it off, they used to have an absolutely ridiculous amount of health and could replace Ticking Spiders in the Basement, though thankfully a patch nerfed their health to only moderately above average.
- Lvl 2 Spiders and Ticking Spiders aren't far behind either. They can move as quick as a regular spider and jump like a Trite (though much less distance), and have around the health of the latter. Ticking Spiders also explode on death, making taking on them from afar the best thing (and still not guaranteed to work) to do.
- Nests are variations of Mulligans that have almost double their health and spawn spiders. On death, they even spawn big spiders or Trites!
- Leapers, the bane of any player going for a No-Damage Run (or playing The Lost). Their erratic jumping makes them hard to hit consistently, they can jump to any part of the screen with little warning, and when there's four of them, the screen tends to be filled with bullet spam from repeated jumps. A real pain to deal with, especially in the original Isaac where lower frame rate makes them harder to predict.
- Mr. Maws. They fling their head at the player if they come close, which can be very hard to dodge due to its speed, and upon death, they leave shooting Maw heads (and sometimes slow-moving Gusher bodies) behind which can be a problem of their own. Even bombs and Brimstone (unless buffed with extreme damage) won't get the head on the first hit. They can be the utter bane of people going for no-hit runs, because there's one room configuration that they are practically impossible to dodge as you enter. Mr. Red Maws are even faster variants which, when killed, leave behind a Red Maw head (which, granted, only fires one tear in each cardinal direction when killed).
- Mr. Mines, stationary Flooded Caves-exclusive variants which launch themselves at nearby players, can burrow underground to pop up in another pit and release six bullets in all directions upon death.
- Psychic Maws. They're a variant of Maws, which are already annoying enemies. These fire homing tears, have increased health, and have an Eternal Fly circling around them which can block hits. Fortunately, they are rather rare, typically only seen in late-game floors like the Cathedral.
- Knights are Goddamned Bats at worst, but there exist two much worse versions of them. The Selfless Knight have Isaac's face in place of the brain and have massively increased speed, which allows them to charge across a room to you in under a second. Bone Knights are a Sheol-exclusive variant which leaves behind a thin trail of creep, making it difficult to get behind them without taking damage (barring that you have an item which grants creep immunity, such as Callus or some form of flight). They gain a speed boost, though they're not as fast as Selfless knights.
- Starting with Rebirth, maroon Champions decay into piles of mush on death that can reform if not destroyed quickly enough, similar to Globins. Although ordinarily only slightly more annoying to deal with than the default version of that enemy, monsters that spawn enemies upon death will spawn that enemy (or enemies) every time they're reduced to mush. If that enemy is a tanky one or if your attack is low, you better hope you've got enough attack power to get through them before the Champion reforms, or you're going to be there a while. A maroon Champion Nest on Cellar I can end your run all on its own if you're not careful.
- Eyes, especially when they're not located in the center. These stationary enemies fire Technology lasers which can cover an entire room and can ignore obstacles, making them highly likely to hit the player if they don't dodge out of the way during the split-second gap where they've locked onto them. Bloodshot Eyes versions are even more dangerous, as they fire Brimstone lasers which persist longer than the Technology lasers and are often situated between rocks, making it hard to hit them (especially without having a weapon to shoot over/through rocks).
- There's even a Stone Eye variant, which constantly spins in a clockwise circle while shooting a Technology laser and will not stop firing until the room has been cleared.
- Repentance adds another Eye variant, the Cathedral-exclusive Holy Eye, which is just as nasty as its brethren. Instead of firing lasers, it shoots beams of light, which are only otherwise used by bosses like Isaac and Conquest and items like Holy Light. And it spams those beams, too, shooting five or six in one volley. It doesn't have a lot of HP, but it's often found hiding behind rocks, shielded by a Bishop, or with duplicates in the same room (thereby filling the screen with even more light beams), meaning it'll take a while to kill either way.
- I. Blobs, Isaac-like varieties of Clotties that behave in a combination of them and Clots: they fire 8-way bullets which makes even diagonal shooting dangerous depending on your items. Fortunately, they are extremely rare, but if you are unlucky enough to see one in a floor, expect to take some damage.
- Chubbers. They have the same appearance as a Vis (the walking stomachs that shoot Brimstone lasers at you) but have a small, invincible Chub housed inside each of their bodies, which fires rapidly, can go through rocks and walls, and takes out a whole heart of health. It doesn't help that they have an insane amount of HP and often come in packs of 5 or 6. Made even worse in Rebirth: their Chub now blocks tears!
- Vis are enemies that shoot Brimstone beams on your direction when they see you. Scarred Vis shoot them on your direction and behind them. But none of them take it to a level as grueling as Scarred Double Vis do. On mere sight of you, they shoot on all four cardinal directions. This leaves very little room to dodge. Keep your wits when you see these specific variants pop up suddenly in The Womb.
- Keepers. They're the little bouncing Greed heads. They jump around erratically like Leapers, put you through Bullet Hell, and every single shot or collision with them makes you drop coins, making one lost forever. Much like spiders, they have the uncanny ability to squeeze between boulders and pits joined by one corner. They often come in packs of four, and Super Greed is all about spawning these.
- Hangers, which are basically hostile shopkeepers. They fire three-way bullets, have Eternal Flies circling them, and have a ton of health. Oh, and taking damage from them also makes you drop coins.
- Masks + Hearts, which are essentially Knights with the brain separated from the body. The Mask is invincible and can only be destroyed by attacking its accompanying heart, which can soak a lot of damage. The masks charge and have very good reflexes, much like a knight, while hearts try to flee from the player, and fire four bullets in the cardinal directions (like the Clotties) to defend themselves if they get too close. Fighting them in rooms with rocks makes them even harder to deal with, and they're rarely alone, often spawning in groups of three or more. Good luck dodging the extremely nimble masks while trying to get a clear shot at the hearts, which retaliate on their own accord.
- Lil Haunt, the mook version of The Haunt, is an extremely cheap enemy. Their movement pattern is designed to lead you, which makes it very easy for them to corner you (but also extremely easy to control them if you know this). They have a bullet attack which has no tell or consistency. They are tougher than most mooks their size. Finally, they make the boss fight against The Haunt that much more annoying.
- Leeches, leeches, leeches. First of all, these little buggers are fast, at least when they notice you. Second, more often than not, they appear in large numbers. Third, they're affected by knockback a lot more than other enemies. While this sounds like good news on paper in that you'll be able to knock them away, more often than not they'll just get knocked into the direction you're currently moving in, making for incredibly hard-to-avoid damage thanks to the aforementioned speed they possess. Oh, and guess what? Leeches can be replaced by two even worse variants - Kamikaze Leeches, which explode on death, and Holy Leeches, which not only sport the death explosion attribute that Kamikaze Leeches do, but they have an Eternal Fly circling around them, which can easily block your projectiles, and it makes their hitboxes bigger, making it more likely that you'll take damage! AAAAAAARGH!
- Wall Creeps have two versions of these that will make you question any choice you make.
- Rage Creeps fire Brimstone lasers. Here's the catch, since the last place you will look an enemy for is the walls (which they reside on), it's very likely you'll want to seize control of the center of the room. However, by that moment, Rage Creeps will likely had fired a beam that you'll be caught on (and sometimes get hit twice by it). And even discounting that situation, they remain very dangerous because their attack has short tell and infinite range.
- The Things (Red Creeps) move at twice the speed of normal wall creeps and shoot a damaging trail of red creep about hallway across the room when they line up to you. It's extremely difficult to kill them without them doing this at least once, limiting your mobility. For an added annoyance, they constantly stick their tongue out when they're lined up with you, increasing the sizer of their hitbox so you can't get as close to them.
- In Greed Mode, any enemy that likes to teleport/tunnel around the room (such as Lumps, Round Worms, and Wizoobs). The double-sized room makes these enemies much harder to track down and kill, which means that they'll often be still alive when the next wave spawns, essentially making you deal with two waves of enemies at a time. And if the Random Number God sees fit to saddle you with multiple waves of these guys in a row, good luck.
- Also in Greed Mode, Death's Heads, the invulnerable enemies that bounce around the room and only die if the room is cleared. The problem with them in Greed Mode is that they only disappear once every enemy is killed, regardless as to which wave they spawned in from. This means that if you can't kill the other enemies in the wave that the Deaths Heads spawn in fast enough (quite likely given that they tend to spawn alongside tough-to-kill enemies like Walking Hosts), you'll end up having to deal with more enemies spawning on top of you, which means more things you have to kill to get rid of the Death's Heads. And the next wave that spawns could very well include even more Death's Heads, at which point you won't have much room to dodge and hitting something that actually takes damage becomes nigh-impossible.
- Afterbirth added a skeletal version of Mom's hand which is approximately 100 times worse than the original. The original just flew down and tried to grab you. This one does the same, only when it lands, sends out several waves of rocks like The Cage, and releases spiders when it dies.
- Afterbirth also gives us the Imp, which is basically what you get if you take a Baby, put it in Sheol/Devil Rooms, give it more health, make it actively try to dodge your projectiles, and make it shoot five times in a row. To top it off, these guys love to hide behind Satan's Statue in Devil Rooms to score cheap shots on you before you fully register the Imp's presence.
- Afterbirth+ has the occasional Mimic Chest. There used to be no way to know in advance if they're spiked chests in disguise until you stand right next to them. Being forced to carefully check each chest when previously you'd just run into them was perceived as an unwarranted annoyance by most players. The design was thankfully changed to feature blood splatter and darker grey colour, making it fairly easy to tell at a glance.
- The Mook Maker Portals in Afterbirth+ quickly became infamous. They're quite common, appear in pairs while surrounded by obstacles or other enemies, and summon a varied assortment of enemies at a fearsome rate. A nerf slapped these pretty hard after numerous complaints, making it so the portal has a chance of expiring on its own after each enemy summoned, made more likely with repeat summons. Still, their existence was contested enough that Repentance went ahead and removed Portals from every floor except the Void, barring a much weaker type in the Mausoleum and Gehenna.
- You know those invincible Death's Heads that bounce around the room until you kill all the other enemies in it? Afterbirth+ adds Stoneys, Fatty variants resembling Grimaces which do an impressive job at being a hindrance. It comes in pairs or large groups and follows you around quickly, providing cover for the rest of the enemies. If those guys spawn at Greed mode, they'll more often than not last until the final wave of enemies and leave you next to no room for avoiding threats. The only saving grace is that they don't damage you on contact. It didn't take long for a Nerf to hit them, making it so they have to catch their breath after chasing you for five seconds, which thankfully degraded them to Goddamned Bats.
- Booster Pack 5 adds in the Cross Stoney, which are essentially Stoneys with a Cross Grimace for a head, which periodically fires four bullets cardinally and diagonally. Thankfully, these are only encountered in the Aprils Fool challenge.
- Repentance introduced Needles, and their variants Pasties, informally known as "Mini-Pins": enemies that burrow underground and periodically emerge to lunge at the player, similar to Pin. The enemies themselves wouldn't be that bad, except for one major detail; nothing indicates they exist in the room until they're leaping out of the ground to attack, which generally takes 1 to 4 seconds. This is fine when they're the only enemies in the room, as the doors locking in a room that supposedly has nothing in it is an obvious clue. However, they can also be in rooms with other enemies, resulting in situations where you're in the middle of fighting them off and suddenly get beaned in the face by a Needle you weren't aware of until right when it attacked. It's incredibly common to run straight into a Needle by accident because you were dodging under the belief that the enemies you can see were the only ones in the room. And to make matters worse, they're everywhere, appearing in 10 different maps and in a whole bunch of rooms. It goes to show you, three things are inevitable in life: death, taxes, and Needles.
- Pasties are even worse because they also shoot tears in the diagonal directions when they emerge from the ground, and are obviously found in Ashpit. But at least they only show up there and Flooded Caves. But believe it or not, it's actually possible for one to show up in a Secret Room.
- Repentance also added Polties, and their variants Kinetis, both brought back from the Antibirth mod. Polties fly around in the room and grab obstacles (rocks, buckets etc.) and throw them at the player. This wouldn't be problematic at all if the trajectory of the thrown obstacle wasn't completely unpredictable. Sometimes, Polties will throw obstacles exactly on your position, but sometimes they will predict how you are going to avoid and correct the trajectory. Kinetis are even worse in that they don't even need to physically grab obstacles, instead they will make them fly towards them (and of course you take damage if you hit the obstacle while it is being moved).
- Repentance has a mulligan variant taking this role. Yes really. Holy Mulligans. Only in the Cathedral these "holy" monsters only summon one thing and that thing happens to the angelic baby which is another difficult monster to deal with. Combine that with the fact that you will likely be dealing with another unholy creature (those leeches.) and the fact that they seem to spawn as many as they want you are in for a ride.
- Gehenna has Goats and Black Goats; of the two, the latter is the worse one. These hellspawns can charge into you without much warning and have the Fallen's same laser attack. They also fly so rocks or the Lost won't help. And to make things worse, they tend to appear in groups of four. Fun!
- Any of the Ascent only monsters can count for their high health.. And the one that has caused the most strife is the Tainted Spitty. High health? Check. Annoying bullets that they fire all the time? Check! Appears with other monsters like Chargers? Check! Never stops firing bullets? CHECK! Pray to Dogma (or the RNG) that these things don't end the Alt Lost run. (If any of the others here don't, that is.)
- Whippers. These creatures have a fleshy tendril that they use as a whip to hit back tears and even bombs if they hit one. The only way to be really safe when pitted against them is to have a long-reaching weapon (like Technology or Brimstone), but that won't always be the case. They also tend to corner you with the help of other enemies in the room, and are fast to boot.
- Snappers are even worse. They're just as fast, but their whip attacks are narrower in exchange for being a lot longer and, to top it all off, pull you towards them in an attempt to keep sapping at you. Worse is that they tend to spawn in the same amounts as Whippers. While Whippers are grueling to go against but their whip strikes' range makes them avoidable, facing the Snappers and getting cornered by them (and the other enemies in the room) can and will put you at the mercy of an (infuriatingly) unavoidable whip strike.
- Cursed Globins are pretty much like the other Globins but with a twist: When they become a pile of ooze, the pile multiplies into a second pile which will reform if they get the chance. Cursed Globins quickly become a battle of trying to stop yourself from being overwhelmed by a swarm if or when things go wrong for you.
- Revenants. A more horrifying variation of their skeleton selves. They don't fire bones but instead spew out fire. They also follow you while they are doing this and come in groups so there is not much place to run when they start. The fire can also go over gaps so flying won't help you here. They also can appear with the Bishops, so you can imagine how well this will go.
- That's before mentioning Quad Revenants, which can breathe fire in four directions at once.
- Bombgaggers. Only appearing in Ashpit, of course. These things spit out a giant bomb known as a Giga Bomb, an explosive that causes the biggest explosion in the game with lots of range to it. And even when you kill them, they spit out the bomb anyways. Hope you got something to protect yourself because they also come in groups. Fortunately, rooms containing these enemies are quite rare to come by.
- If you have the Safety Scissors trinket, these Giga Bombs will not blow up after spawning, and will instead become a collectible pickup. With this, you can farm 99 Giga Bombs to use against other enemies and bosses yourself!
- Gutted Fatty. These things use their guts to attack you by ejecting them out of themselves. Their guts spawn Chargers, they are VERY tanky, and the worst part is that as you attack, their eyes (which won't die till they do) pop out and follow you around. And when they die, any guts will still live and keep spawning Chargers.
- Psy Tumors, who begin to appear in Cathedral. You know those enemies that look like a cloud with a butthole who spit projectiles in all directions, like, non-stop? These ones shoot homing bullets. Your tactic to fight these guys is either pray you have cover of some sort, or hope you can kill them before they drain all your health. If you encounter a room full of them, you're basically SOL.
