The Elseworlds graphic novel Batman: Crimson Mist ends with every named character in the Batman world, except Dr. Jeremiah Arkham and, apparently, a female expert in the supernatural, killed off.
Coheed and Cambria: The Amory Wars — The Second Stage Turbine Blade. Not only do Coheed and Cambria get tricked into brutally murdering their own children, they also die mostly because Cambria destroys a spaceship's engine in a fit of rage. Secondary characters also die in a failed coup, by the truckload. And that's just one of the chapters in the story!
To make matters worse, Claudio (the protagonist for much of the storyline followed SSTB) is supposed to destroy the entire solar system, and release the souls of the Keywork!!! (The Keywork is the fictitious Solar System thing). Because Destiny Says So.
In the final two issues of Combat Kelly and his Deadly Dozen, almost all the members of the Dozen are killed when a mission goes disastrously wrong, with the only survivors being Kelly and Laurie (and Laurie is permanently crippled).note Two members of the team—'Snake-Eye' Simpson and 'Mad Dog' Martin—are not shown as being on the mission so presumably survive. Their fates are not mentioned, however.
Doom Patrol pre-dated most of this by pulling a Total Party Kill in the Sixties. All four of the actual members (The Chief, Rita Farr, Cliff Steele, Larry Trainor) were nuked saving a small fishing village.
Fables: The last issue of Jack of Fables kills off everyone but the baby and the black guy.
Gotlib drew a Hamlet parody. The source material being what it is, it ends with all named characters death. The doctor who diagnoses all deaths as viper beat (yes, even Ophelia's) dies beaten by a viper. The gravedigger has an heart attack seeing all these corpses. Then the narrator shoots himself.
The Great Lakes Avengers have a nasty habit of losing members, including Mr. Immortal's love interest in issue 1.
Probably the only safe characters are Mr. Immortal (whose power is Exactly What It Says on the Tin; he absolutely cannot be killed by any means, not even by completely obliterating his body) and Squirrel Girl (who's too popular to kill).
Actually, they honestly haven't gotten it nearly as bad as one might think from the way their first Dan Slott mini parodied the kill-happy nature of major comics crossovers. The only long-term member who has died and stayed dead is Dinah Soar; Doorman died but came back as an angel of death, and Big Bertha and Flatman are still alive and kicking. Aside from that, you've just got characters who were essentially created by Dan Slott to die.
The Infinity Gauntlet featured Thanos using the title object to wipe out over half of the universe's population in order to impress Death, which includes several major and notable supporting characters from various Marvel books, like the Fantastic Four, the original X-Men members (then known as X-Factor) save Cyclops, Mary Jane Watson-Parker, and Rick Jones. Then halfway into the storyline when the surviving heroes band together to form one last stand against the power-mad titan, it doesn't end well. In the end a Reset Button winds up restoring everything back to normal.
The Legion of Super-Heroes storyline "End of an Era", which rebooted the Legion, ended up by killing off everyone from the old history before restarting history.
The Marvel Mangaverse "Rings of Fate" arc (which also was the Series Finale of that set of comics) wound up killing a good chuck of it heroes and some villains leaving only a handful left standing.
Pride of Baghdad ends with all four protagonists being gunned down by American soldiers without even achieving the freedom that they'd been dreaming of. It should probably be mentioned that the protagonists are lions.
The final issue of The Protectors and the rest of the Genesis universe from Malibu comics before Ultraverse has everyone including its universe killed off with a bang as the Earth was pulled apart via interdimensional portals, killing absolutely everyone.
Also The Punisher: The End from the MAX imprint, where after a nuclear apocalypse, the Punisher and his sidekick venture out of a bomb shelter when the radiation has gone down enough for him to make it to the people responsible. He kills them, then his sidekick (who was actually a murderer), and then dies.
Punisher: My first instinct was to kill everyone there. So that's pretty much what I went with.
The main MAX series kills off characters frequently, and by the final arc, "Homeless," most of the major characters in the series are dead, including Frank himself. The final issue then kills off the two remaining notable characters still alive, with Nick Fury being the only supporting character still breathing.
Rising Stars is about 113 people with superpowers, called the Specials. At the end, they're all dead. The two most important non-Special characters also die.
Strikeforce: Morituri is literally this trope. To combat an alien invasion Earth develops a process for giving humans superpowers. The process is uniformly fatal within a year to all who undergo it. If they aren't killed in combat at some point they will just one day die. Horribly.
Sunpot, a comedic science-fiction comic by Vaughn Bode (originally serialized in Galaxy Science Fiction Magazine and later reprinted in both a one-shot underground comic and in Heavy Metal). Frustrated by censorship and disagreements with the editors of Galaxy, Bode abruptly ended the series with a final episode showing the entire crew of the spaceship Sunpot lying dead in the wreckage following an off-panel disaster. To emphasize the finality, the last page was a splash panel showing the derelict ship floating in space, with a large caption declaring "Sunpot Is Dead."
The Teenage Mutant Ninja Turtles Adventures spinoff "Mighty Mutanimals" ended with the entire team, including animated mainstays such as Leatherhead, Slash and Metalhead, assassinated.
The Transformers (Marvel) featured vast numbers of deaths. In fact, something like 1/5 of all the characters introduced in the comic series had died by the end (in the case of Optimus Prime, twice over, but everyone else was for real). In fact, sometimes characters who had been the focus for multiple storylines with them evading death multiple times would suddenly be killed with no warning in a very off-hand manner several years later, most notably Blaster, who had something like two years' worth of storylines based around him during which time he was repeatedly shot, infected with a horrific robotic illness, at one point completely disassembled and then tortured non-stop for months on end by Grimlock before finally getting some semblance of a normal life, only to be killed a year later by Starscream without a second's thought.
This trope then went insane in the Transformers: Generation 2 sequel series in which the corpses mounted up at an alarming rate.
The later Universe comic introduced a gigantic number of characters in the first issues. This was way more than could be properly handled, so they massacred most of them until it was at a better size.
Simon Furman would be brought in to write the series finale for Beast Wars. His first question to the staff? "Who can I kill?" The answer? Tigerhawk, Depth Charge, and every Predacon except Megatron and Waspinator. Every character that Furman kills off that gets a death scene of their own concludes it with the line "Oh well. Never did want to live forever!"
"The Underbase Saga", in which a cosmically-powered Starscream killed most of the cast from the comics, Autobots and Decepticons alike, was written by Bob Budiansky as his final story arc before he left.
Usagi Yojimbo author Stan Sakai wrote a Kill 'Em All Final Battle as an experiment, but decided it was "too depressing".
At the end of the prison arc in The Walking Dead, every single character present during the attack from the Governor, including a baby, is brutally murdered, save for Rick and Carl.
What If? is often known for doing this in several of its issues, usually ones that show what the downer outcomes to major events within the Marvel Universe could have been like.
X-23: Innocence Lost, the Origin Story for X-23, has a cast of about a dozen named characters. By the end, all but four of them are dead. And of the four survivors, three had very little panel time. This doesn't even count the dozens more nameless Mooks and other victims we see X kill either in her final rampage to escape the Facility, or over the course of her missions.
The comic kills off team members intermittently throughout the series, before slaughtering the survivors en masse in the final issue. Still managed to have a sequel series, by showing some of the characters' fates in the afterlife.
Despite being violently killed along with his teammates, Doop turned up alive in Nation X.
X-Men featured at least one story arc which took place in an alternate future in which Sentinels had killed most of Earth's heroes and enslaved the rest. By the end of it, the adult Shadowcat is the only X-Man alive. Though Rachel Summers managed to also survive via Time Travel, and now lives in the main Marvel Universe.
There's also the Age of Apocalypse, an alternate timeline where Professor Xavier was killed years before he would've formed the X-Men, and Apocalypse takes over half the world and has already killed off most of the population. It goes downhill from there.
