Ultron started out as Hank Pym just tinkering around in his lab. Flashbacks revealed his original appearance looked about as threatening as WALL-E. Then he rebuilt himself a skull face and glowing red eyes...
Nobody AIM scientist plus hideous experimentation equals M.O.D.O.K..
Black Widow: Natasha Romanoff by most accounts was just a little orphan girl found as a baby, the fact she went from that to The Dreaded super spy assassin turned superhero who fights alongside gods is pretty amazing. Though it’s implied given her surname of Romanoff, that Natasha may come from Russian royalty and another comic has the Asgardain goddess Enchantress give Nat her blessing when she was a girl, so it’s equally possible Natasha was actually always meant to be someone very important.
The Red Skull started his life as a poor starving orphan named Johann Schmidt. Growing up in post WWI Germany as a petty thief, he eventually landed a job as a bellhop in a classy hotel. One day, he was performing his duties as a bellhop when he happened to be in the same room as Hitler himself while the latter was berating an officer. After seeing Schmidt, Hitler exclaimed he could turn the bellhop into a better Nazi than the officer. He did.
Captain America himself would qualify as a heroic example. Born to poor Irish immigrants in the Lower East Side, Steve Rogers was but a humble, scrawny fine arts student when he volunteered for a Super-Soldier project that turned him into the ultimate weapon against the Axis Powers. Today, he is the most respected hero in the Marvel Universe and the bane of Nazis everywhere.
Captain Britain: In his first appearance, Mad Jim Jaspers was a gimmicky Harmless Villain who ended up effortlessly trounced by the Captain and completely forgotten about. A few issues later, he reappears and unleashes his reality-warping powers, conquering first Earth and then the entire universe, bending it to his twisted will and reducing its inhabitants to utter insanity. And Captain Britain is powerless to stop him.
Victor von Doom was the son of a Romani couple, though they were related to deposed former royalty. Things went awry when his mother sold her soul to the Devil and died when he was young, and he was raised by his father and a group of Roma. But the local barony demanded his father to use his intelligence to cure his dying wife's incurable disease. The fact his father wasn't able to save her, caused his father to go on the lam with Victor, and severe frostbite cost him his life. From that point onward, Victor von Doom used his intelligence to get a leg up in life, and when someone proved just as smart as he was ... he became Doctor Doom. Then he breaks the multiverse as Rabum Alal.
One of the biggest examples from Marvel Comics is Galactus, the Devourer of Worlds, who began his life as a simple mortal explorer trying to figure out what was going on as his universe ends around him... after merging with the cosmic egg, he is reborn in the new universe as one of the nigh-omnipotent embodiments of existence, feared throughout the entire universe by every civilization that knows he exists.
The Hood: Parker Robbins was a loser and small-time crook, until he stole a magic cloak and boots. As the Hood, he quickly rose in rank in the criminal world, until turning into the leader of a gang strong enough to butt heads with The Avengers and live to tell the tale, gaining himself a place in the Cabal.
At one point other supervillains wonder why exactly they follow him and his cousin calls this trope - they all started as nobodies before becoming superpowered crooks, but they had normal lives, while Parker was the only one to start from the bottom and knew what to do to crawl his way to the top.
Unfortunately, this ultimately got Robbins addicted to power for its own sake. When he lost the cloak and boots, he desperately scrambled for new super powers since he can't bear going back to being a nobody.
The Leader was originally a mentally handicapped janitor at a deserted army base.
The Hulk himself is an example of this, though a more heroic and sympathetic one. Bruce Banner started his life a bullied and dogged weakling overlooked by everyone (save for a couple of people like his mother Rebecca, cousin Jennifer and Betty) even when becoming a accomplished scientist Bruce was still considered a pen pushing waste of space. After being bombarded with Gamma Rays and Hulking Out, very soon “Puny Banner” became the strongest being in the multiverse who can throw down with gods and smash time itself. Played With though, as according to the One Above All, Bruce was always meant to be a big green badass force of nature.
The Mighty Thor: Gorr the God Butcher used to be a poor starving mortal. After acquiring All Black the Necrosword, he became a god-killing abomination who singlehandedly wiped out entire pantheons across the cosmos.
In at least one alternate future, Victor Mancha is destined to become Victorious, a dreaded, mass-murdering super-villain who slaughters the Avengers. But in the present, he's pretty much the designated Butt-Monkey of his team.
The Runaways' original enemies, The Pride, were all a bunch of nobodies and small-time crooks, until they were summoned by a trio of monstrous descendants of fallen angels who offered them work. Since then they have been a criminal organization that controlled underground activities on the West Coast yet managed to stay undercover in the Marvel Universe for years, were respected by such powerhouses of crime as the Kingpin or the Hellfire Club, and at one point gave the Marvel Illuminati — a group composed of Iron Man, Reed Richards, Black Bolt, Doctor Strange, Charles Xavier and Namor the Sub-Mariner — a run for their money.
The Jackal: Biology professor who fancied Gwen Stacy.
Green Goblin: There have been three villains with this name — an inventor and businessman, a college student, and a psychiatrist. The third, however, did prove to be ineffectual.
The first Hobgoblin, a villain modeled after the Green Goblin, was a fashion designer. For a while, he had a mild-mannered reporter brainwashed to pose as the Hobgoblin as well. This trope was averted with the second Hobgoblin, however, who was a previous mercenary and supervillain Jack O' Lantern.
Spidey himself is a heroic example. Like the aforementioned Bruce Banner, few could have guessed that pathetic geek from Queens would take such a level in badass and be a hero that other heroes (even Captain America) praise and be inspired by nor that he’d be someone who willingly fights powerful aliens and gods when needed, which is quite a step up from getting pushed around by Flash Thompson.
Ultimate Fantastic Four: Reed Richards started out as a bullied teenager mocked for his intelligence, became a superhero, but after growing out of favor with the way the world is run, decided to take over the world, and now he's The Maker.
Wolverine: Wolverine is a more heroic example: he started his life a Delicate and Sickly little boy whose caretakers believed wouldn’t last long in the world. Yet that meek and fragile child became one of the biggest grizzled badasses in Marvel; he lost his sweet innocent nature but being the dreadedberserker certainly made up for it. Worth noting Logan wasn’t technically a total nobody, being the heir to a wealthy family; if his life hadn’t taken a cruel swerve towards the uncanny, he theoretically could’ve had a cozy life, if his father hadn’t been killed and he didn’t pop those claws.
X-Force: Eli Bard went from a soldier to a respected Roman senator — until his wife stabbed him in the back. After that he went from a destitute ex-senator to vampiric monstrosity who not only commits mass murder but manages to overpower some other genuinely badass individuals.
Professor X is another more heroic example of this, he started off as just a pampered little boy bullied by his stepbrother and abused by his drunken stepfather. It’s incredible to think that boy would became one of the most powerful beings in existence and the figurehead of mutantkind or the leader of his own nation.
His son David aka Legion is an even better example, going from abandoned mentally addled little boy to multiversal Reality WarperPerson of Mass Destruction in the span of a couple decades.
Jean Grey: Suburban girl with Carrie problems to mutant messiah.
Cyclops: Foster home kid to mutant Captain America.
Gambit: Doorstep Baby to one of the most baddass mutants ever (and would become the most powerful mutant if Mister Sinister didn’t limit his abilities through surgery).
Subverted with Storm, she was this originally being an orphan street urchin in Africa who became worshipped as a goddess in Kenya for her Weather Manipulation mutation. But similar to Scarlet Witch, later comics retcon that Ororo was predestined to be this way, being descended from an actual godhood on her mother’s side.
Scarlet Witch and Quicksilver were just poor Romani children drifting around with no place to call home. The fact they became such powerful individuals given their humble origins is incredible. Though averted later as it was retconned that they were predestined to be that way with their mother Natalya being the Scarlet Witch from a long line of Scarlet Witches.
Max Eisenhardt was just a poor boy who had the terrible luck of being born into a Jewish family in Nazi Germany. After a truly tragic Start of Darkness that started in the Death Camps and ended in an America entrenched in racism, Max is no longer a boy but a very angry man who not long ago discovered he possesses incredible powers. He's also assumed a few aliases along the way; the latest one? Erik Magnus Lensherr, a.k.a. Magneto.
Sabretooth and Mystique were even bigger nothings than Magneto who at least came from a middle-class family, Sabretooth was a Tom Sawyer-esque Canadian hick and Mystique was an abused runaway child. Few could have guessed they both grow up to be two of the most dangerous mutants in existence.
◊, and almost succeeds in killing a Russian mob boss. He only fails because Spidey talks him out of it.
