Civil War (2006): The entire mess started due to the New Warriors storming a house containing a group of fugitive super-villains in the middle of suburbs of Stamford as part of a reality TV show. This provokes Nitro to blow up, causing extensive property damage and killing 600 civilians, including 60 children at the elementary school across the street. As a result, the disapproval of unlicensed, untrained superhumans increased which convinced Congress to pass the Superhuman Registration Act. This divides the superhero community into pro-registration and anti-registration factions culminating in Red Skull's assassination of Captain America and the rise of Norman Osborn's Dark Reign.
Deadpool is this in a very large way in Secret Empire: Steve Rogers has been cosmic-cube'd into a Hydra agent and Wade started working for him without knowing this. During that time, S.H.I.E.L.D agent Phil Coulson figures out what happened, but before he can warn anyone, he is assassinated by Wade on Cap's orders. With Steve's cover intact, Hydra's plans proceed unchallenged, and they take over America and trap Manhattan under a dark-force dome. Wade mentions in chapter 32 that he didn't know Cap went Lawful Evil until after he joined him. He tells Preston the same in a flashback in chapter 33, admitting he didn't know any of the following would happen -like the dome over Manhattan.
In FF #5, Reed and Susan's children Franklin and Valeria viewed a set of holographic wills their family left them. Ben confesses his deepest darkest secret in his: back in college he was pissed off by a certain Jerkass who kept mocking his best friend Reed. So one day Ben snuck into the guy's room and messed around with one of his experiments... This is a doubly appropriate example given the moniker the guy would start using after that day.
Having used a Xanatos Speed Chess style plan to save the world a few times, Kid Loki find out, to his horror, that pretty much everything he's done during Journey into Mystery (Gillen) has come back to bite him in the ass all at once — the main villain of the Everything Burns crossover is Surtur, who was originally released by Loki, he's aided by The Manchester Gods, who gained their power with Loki's help, and Surtur's herald is the alternate version of Leah that Loki had written into the Serpent's backstory. Right after he clears all of that up, he discovers that Mephisto, still angry at Loki for releasing the Disir from their curse, has found out about the Fear Crown that he'd created and is going to use it to create a literal hell on earth. Unlike a lot of examples here, because he's the protagonist, it comes across as being more tragic than annoying — no matter what he does, something's going to come along and ruin his happiness and success.
When Magneto first manifested his powers, an angry mob burned his house down and prevented him from saving his daughter Anya from a fire, causing him to use his powers to murder them all and permanently estranging his wife Magda. It's the first time Magneto takes a life, but not the last...
While pursuing Magneto-worshipping mutants to Asteroid M, a S.H.I.E.L.D. agent shoots one of them, who nearly dies in Magneto's arms. This triggers another Face–Heel Turn from the formerly-retired Master of Magnetism.
At the same time Magneto found out Moira MacTaggert had been tinkering with his genetic code, apparently attempting to force him to reform. To call him "displeased" would be an understatement.
In response to Magneto's later return, the governments of Earth surround the planet in a satellite shield that will prevent Magneto from returning to Earth. In response Magneto EMPs the entire planet, causing catastrophic casualties. In response to that the X-Men attack Asteroid M, ultimately leading to Charles Xavier mind-wiping Magneto and creating Onslaught, who nearly destroys the planet and does temporarily kill of most of Marvel's superheroes. All because the Earth governments launched a pre-emptive defense against a man who was, at the time, content with splendid isolation.
Magneto is later (publication-wise) targeted by Legion, Xavier's son, who believes killing Magneto before he can get started will bring about the utopia his father always wanted. Legion screws up and kills Xavier instead, resulting in the Age of Apocalypse.
Magneto finally catches the short end of the stick when Cassandra Nova convinces Donald Trask III, Bolivar Trask's last living relative, to reactivate a South American Sentinel program and attack Genosha. Trask is a dentist who seems too stupid to understand the full implications of what he's doing, namely murdering 16 million mutants.
Emil Gregg was a mentally disturbed compulsive confessor who, unwittingly, was living next door to Stan Carter, aka the murderous Sin-Eater. Overhearing Carter's taped ramblings, Gregg convinced himself he was the Sin-Eater and began reporting details of the killings to reporter Eddie Brock, who began a series of hit stories about him. When Gregg was arrested, Brock wrote his masterpiece...and an hour after it hit the streets, Spider-Man caught Carter and exposed Gregg as a fraud. Humiliated and disgraced, Brock lost his job, his wife, and his self-respect and blamed it all on Spider-Man. He was then found by an alien symbiote who also hated Spider-Man and together, they formed a new twisted being. In short, thanks to one pathetic man's need for attention, the world got Venom and a few years later, Carnage.
X-Men villain Mastermind when he turned Phoenix into Dark Phoenix. He thought he was merely brainwashing Jean Grey and capturing the X-Men as part of his bid to join the Hellfire Club's Inner Circle. Neither he nor the rest of the club realized they were messing with a cosmic entity and ended up putting the entire universe at risk.
First X-Men has Victor Creed's then girlfriend, Holo die, and he blames Wolverine for convincing her to stay and fight with him. But that shouldn't be a big deal for Victor, who is over one hundred years old, and they only had a short relationship, right? Well, when she was mortally wounded, she used her powers to show Victor an illusion of the two having a family and living a long, fulfilled life, and he thought that was what was happening and experienced it first-hand, and she told him that this is what he should remember... before cutting the illusion and revealing that she was actually still mortally wounded. She tells him that it "doesn't have to mean anything less". Well, he took this to heart, and determined that it logically meant that Logan had taken it all away, and would spend the rest of his life ensuring that Logan would never find anything or anyone worth living for ever again. So it's less "you got my short-term girlfriend killed" and more "you took away my happy ending". On that day, Holo's nice little parting gift and last words created an archnemesis for Wolverine that would go on to menace him and everyone around him for the rest of his life. And they're both immortal.
Captain America was a successful Super-Soldier made back in WWII, but there were No Plans, No Prototype, No Backup, and no more super-soldiers could be made since the death of both Rogers and the creator. Attempts to recreate the super-soldier formula turned out wrong in several cases: Hulk (an out-of-control monster), Green Goblin (basically a controlled Hulk, but by an evil and amoral man), Frank Simpson (a super-soldier that went rogue in Vietnam), etc. The Soviets also tried, but kept all their failed experiments locked and forgotten inside a bunker. Even mutant themselves were the result of the attempts to recreate it.
The Ultimate X Men somehow managed to escape to the 616 universe after Secret Wars. They were captured by Ms. Sinister, who used them for her experiments, as seen in X-Men: Blue. She created the Mothervine from the unique type of mutations from the Ultimate Marvel universe, which of course became a huge disaster.
In a case of both sides doing this to the other, Ted Sallis met with Curt Connors met with after the latter recently lost his arm and both discussed their respective work, Sallis's work to recreate the Super-Soldier serum that made Steve Rogers into Captain America and Connors's desire to find a way to regenerate lost limbs — the same research that'd lead Sallis to become Man-Thing and Connors to become one of Spider-Man's enemies, the Lizard.
Lawful Evil until after he joined him. He tells Preston the same in a flashback in chapter 33, admitting he didn't know any of the following would happen -like the dome over Manhattan.