Long time on again/off again X-Men antagonist/ally Magneto arguably fits this trope, having suffered through the discrimination of World War II as a boy only to face it again as an adult for being a mutant, though he's better known for being a Well-Intentioned Extremist.
Madelyne Pryor learned that she was a clone of Jean Grey and was abandoned by her husband, Scott Summers (who fell in love with her because of her obvious similarity to Jean, though neither knew she was a clone at the time, assuming it to just be mere coincidence that they looked exactly alike), when he reunited with Jean, after Jean returned from the dead. Then Maddie's infant son was kidnapped and she was left for dead. She has a daydream where she's ripped apart to build the woman her husband actually wants and then is offered revenge. Thinking that it's just a dream, she accepts, which, naturally, leaves her possessed by a demon and willing to sacrifice her baby (who she finally has the power to find) to allow the demons of Limbo to take over the Earth.
The Scarlet Witch undergoes a fluctuating life where the good (a family with The Avengers, marriage to her One True Wuv, having her longed-for kids) is outweighed by the bad (her father is a supervillain, her husband gets mindwiped and divorces her, her kids aren't real), along with a number of possessions, kidnappings, and multiple forced amnesia inflicted by her most trusted friends. Then she rewrites the universe. Then she does it AGAIN.
Green Lantern villain Atrocitus. His entire space sector was wiped out by the Manhunters, and the massacre is enough to drive his anger to the point where it gives birth to the Red Lanterns. Not even the other characters realize just how painful seeing the massacre was until they visit his dead home world. "The Manhunters came and we... We did nothing to deserve this. We...we did nothing.
"He loved something once... life."
He even shares a brief moment of empathy with Saint Walker. Saint Walker admits that he, too, was once filled with rage after losing his entire family to random accidents during a pilgrimage. Only a brief moment, since Atrocitus points out one crucial difference: Saint Walker had no one to blame for their deaths, while Atrocitus can and does blame the Manhunters' creators, the Guardians.
All of the Red Lanterns are like this to one extent or another, since Atrocitus specifically looks for rage "driven by loss" when recruiting. Earth's representative, Dex-Starr, for example, is a housecat who witnessed the brutal murder of his beloved owner, then was put in a sack and tossed off a bridge. One was a woman whose husband was killed by the Sinestro Corps, she was imprisoned on Ranx and was repeatedly raped by the various Corps members.
The one exception to this is the newest member of the Red Lanterns as of Brightest Day: Lobo.
The Rage Entity Butcher's chosen host before it was sealed by Atrocitus was a man whose daughter was recently murdered.
And before it was retconned that he was possessed all along, Hal Jordan became this while he was Parallax. During that time, the other heroes tried to show to him that they could understand his loss and his pain, and convince him to turn back from the path he had chosen as they stood against him to protect the universe.
"What if the Avengers had become the pawns of Korvac?" (What If? v1 #32) ends with a giant Korvac sitting on Earth in a state of bottomless despair, holding the Ultimate Nullifier. He thinks of everything that ever was, is, and will be, and presses the button.
The Joker in the Emperor Joker storyline. He decided that any universe where not only his tragic past (whatever that was) could happen, but a guy like the one he became could be left alive and allowed to run rampant...well, a universe like that didn't deserve to exist.
In the last story arc in Captain Atom, Nathaniel Adam creates his own universe where he gets to control everything and create an ideal life for himself, one in which he never became Captain Atom. Being human, he then governs that universe so badly that he loses control of it to his own dark side, who forces him to relive his childhood in which his father left his fall-down drunk of a mother who proceeded to kill herself and his older sister, who had raised him. Finally, Cap is forced to destroy his own universe to stop his evil side. An unusual example in several respects: first, Cap is a hero; second, he succeeds in destroying his universe; and third, it had, by that point, become so monstrously horrible that destroying it was the right thing to do.
He picks up more experience than he'd like later on: during the Wildstorm crossover Armageddon, he gets trapped in the Wildstorm Universe in such a way that he cannot leave and will eventually blow up, killing everyone in the Wildstorm universe. He does everything he can to prevent this from happening, but while he does eventually get cured and sent home, Nicola blows up the universe instead, but also recreates it in its post Infinite Crisis incarnation.
Caliginous in Hero Squared has decided that life is nothing but pain, misery, cruelty, and death, and should be ended in preferably the most all-encompassing fashion possible. Her arch-nemesis, Captain Valor, just sees her as an evil megalomaniac, but his alternative self, Milo, manages to recognize that, beneath it all, she's a broken, lonely, psychologically tormented, and suffering woman.
A Marvel What If? shows us an alternate universe where Tony Stark fires satellite lasers at the Hulk during World War Hulk, killing every superhero present except for the Hulk. The Skrulls see the Hulk as their prophet and launch their attack early, killing most of the other heroes and conquer most of the planet within two months. The Hulk is recruited into the resistance, makes great progress, and becomes a symbol of hope and inspiration. Then the Skrulls hit the heroes with a bioweapon, killing them all— once again, except the Hulk. The Hulk, now utterly bitter and filled with nothing but rage, summons the Silver Surfer to have him call Galactus to destroy the earth and the whole Skrull population with it. Once this is done, the Hulk becomes the new Herald of Galactus, the World Breaker, and goes on to destroy countless other worlds by feeding them to his new master.
Scarecrow, anyone? Victim of a Prank Date, bullying throughout his school years, absentee parents, and an abusive grandmother with trained crows to attack him for the slightest mistake, no wonder the poor kid became obsessed with fear.
From Bad to Worse in Blackest Night. Due to being exposed to too much of his own fear gas, he can't even feel fear. Or nearly any other emotion anymore, except when facing Batman. Yeah, it means the Black Lanterns don't consider him a priority target and he brought it upon himself, but it's still a raw deal.
Joey Finklebarr, in Freak Force, is a boy who wakes up with super-strength and invulnerability. Once picked upon, he proceeds to murder his schoolmates and his abusive father. He is all but unstoppable, but gets talked down by Savage Dragon on the brink of total nihilism.
Shrinking Violet, the insecure wallflower of the Legion of Super-Heroes during the period that she was under the influence of the Emerald Eye in the Postboot continuity.
The Boys has recently gone into this territory. Butchers response after finally having revenge on the man/superhero who raped and indirectly killed his wife kill every superhero in the world. A superhero raped his wife who in turn did not tell him about it. Several months after the event the fetus from this rape grew exponentially and clawed its way out of her womb, killing her in the process.
Homelander turns out to be one. He only became a monster because of a horrific gaslighting campaign courtesy of his own clone Black Noir that convinced him he was already a hopelessly insane baby-eating rapist-murderer. Seeing photos of himself committing heinous crimes that he couldn't remember made him snap. Butcher remarks that Homelander became a psychopath by accident.
X-Force once faced a villain team called the Inner Circle, two-thirds of which were this trope. For starters, they all have uncontrollable powers related to death, which is bound to cause some angst. Individually, Eli Bard was a loser through his whole life, then was vampirized by Selene and forced to be her slave for the next two thousand years; Wither lost many of his friends (including the girl he liked) to crazy religious fundamentalists and later his surviving friends abandoned him for being "dangerous" (oh, and later he's vampirized, too); Blink was abandoned and left for dead by the X-Men after saving all their lives (to be fair, they Never Found the Body); and Mortis had an abusive father while her half-sister, Dazzler, had a loving one and grew up to become a famous singer. Selene gave them refuge and taught them to do whatever they wanted with their powers... which resulted in lots of people dying. While by the time of the final battle they're all ranting-and-raving Omnicidal Maniacs, that, if anything, makes their situation even more tragic. The two exceptions in the group of six are Senyaka, who signed up to have better opportunities to kill people (fittingly, he's also the one with the best control over his powers and the only one who was a villain before being recruited by Selene), and Selene herself, who just wants to become a goddess.