Recurring Teen Titans character Deathstroke the Terminator a.k.a. Slade Wilson started out as a ruthless, though not unscrupulous assassin who honestly didn't have any great animosity towards the team and originally only came into conflict with them as part of fulfilling a contract that his son died trying to complete. When he dropped the contract he actually became rather amiable towards his former targets, actually counseled grief-stricken members of the team on occasion, and teamed up with them fairly regularly. While his relationship with the team eventually went sour again, it really doesn't explain him suddenly becoming a Card-Carrying Villain and doing things like injecting his only surviving child with a Psycho Serum and implanting a chunk of radioactive kryptonite in her eye socket and nuking Bludhaven to spite Nightwing (a character he had previously had a lot of respect for). When pressed for a reason why he'd become such a monster his only answer was because he blamed Nightwing and the Titans for all the loss he's experienced in life, namely his children dying/abandoning him, despite the fact that it had been established that his sons had died under circumstances out of both the Titans' and Slade's control and his daughter abandoning him was unquestionably his fault. Since then, Deathstroke has engaged in nothing but wanton villainy. Nightwing actually calls him on all of this.
Perhaps not so coincidentally, Deathstroke's shift into a Card-Carrying Villain happened around the timeframe the Teen Titans animated series debuted, wherein Slade's character was more-or-less a Card-Carrying Villain from the start and likely contributed (albeit negatively) to the characterization of his original comic book counterpart.
To be fair to Deathstroke, he'd already become plenty unstable during his own series, which took place during The Dark Age of Comic Books. Then his demon-possessed son Jericho (whom he'd had to kill years earlier) took over his mind, spent months tormenting him with every hideous thing he could imagine (and vice-versa), and forced Deathstroke to kill his Morality Pet Wintergreen and mount the man's head on a plaque.
Following the reboot, Deathstroke is a Consummate Professional who's concerned with maintaining his reputation as he gets older. No connection to the Titans, though he still can't maintain a decent relationship with his family.
Aaand following the re-reboot, and his memories of the original Titans returning, he hates them again. Although his motive in targeting them isn't simple revenge it's altering time to get Grant back.
In an issue of Spider-Girl, there's reports that Magneto's been spotted (despite disappearing some time ago), and everyone's on high alert, with the X-Men, Avengers, and Fantastic Four on the lookout, cautioning anyone to call in back-up if they see him. When Spider-Girl and a young X-Man spot what looks like Magneto, they quickly come to the conclusion that it's just someone posing as the powerful mutant because, come on, would Magneto really be robbing a bank? They're right, and go at him alone in order to spare him the utter beating that would result from every hero in the Tri-State Area dropping on his head.
Similarly, in Spider-Man, Doc Ock bobbed up and down from wanting to complete his life's work, world domination, petty thievery, and just wanting revenge on Spidey for past humiliation. Usually excused by the fact that the accident made him plumb crazy, and the AI in his arms was screwing with him. Plus his short foray into trying to cure AIDS! To be fair, in-universe it was believed that he was trying to create some form of biological weapon. Only the readers knew that he was searching for a cure purely to save his first love.
There was one comic where Ock had a rival who'd stolen his design for the arms. There was a three-way battle between Ock, Spidey, and the rival in a hotel, and when the rival took out some support columns Spidey tried to get people out. Ock braced the falling ceiling and got people out - but then let it fall on Spidey and went off to get at that rival. He never lost sight of his objective and went into "get Spider-Man 'cause I'm a bad guy and that's what bad guys do!" mode. It seems he's gotten out of this. Of course, he'll be back again, and will need a reason.
In a rare positive version of this trope, Lex Luthor, Superman's Arch-Enemy, started out wanting revenge on the Man of Steel for making him bald (yes, really. This happened in the Silver Age, when goofy motivations abounded...) even though it was also because Superman accidentally destroyed his lab as well as the lifeform he created which Luthor attributed to jealousy. Nobody complained much when this motive decayed away, even though none of its replacement motives for being Superman's nemesis are as clear-cut. Lex himself would tell you that he's doing it to prove to humanity that they don't need an alien savior and that when Superman is gone and humanity rules itself again (with Lex, as the smartest and best human, naturally in charge), he'll use his genius to cure cancer and rescue kitties and make the world wonderful. Superman would counter that by pointing out that he was gone, for a year (and until he came back, it seemed like he'd be gone forever), and Lex spent the year... plotting ways to kill Superman.
Grant Morrison's All-Star Superman gives Luthor's obsession with beating the Man of Steel a simple explanation that in hindsight makes complete sense: If it wasn't for Superman, Luthor would be running the planet.
Another Superman villain, the Silver Banshee. Originally she came to Metropolis from Scotland to retrieve a book that was payment for her powers. Eventually she got the book, was dragged into the underworld, brought back, and promptly vanished. Now whenever she appears she causes random problems for no real reason.
When she guested on the Smallville episode Escape, Clark points out that the people who wronged her have been dead for over a hundred years, so her revenge is already complete, and that her killing random people doesn't accomplish anything. She answers, "Maybe, but it makes me feel a whole lot better." Then she attacks him.
The Spider-Man villain Venom could be said to have lame motivations from the start, wanting revenge on Spider-Man for exposing the truth about Eddie Brock's shoddy reporting when he should have arguably done a better job himself. This trope is inverted in the various screen adaptations of the Spider-comics, as both the 1990s cartoon and The Spectacular Spider-Man cartoon, as well as the Spider-Man 3 movie, all take their time to build up Peter Parker's animosity with Eddie Brock, giving him more and better reasons to hate Spider-Man than he ever had in the comics, and making their animosity more personal. In the original comics, Eddie Brock was unveiled without much buildup, but subsequent takes on the Venom character develop Eddie Brock on his own, before any contact with the symbiote.
In the comics, it morphs into that Eddie decides that pre-symbiote, he was innocent and Peter screwed with all that by destroying his career. Eddie decides to go off and protect innocence in all its forms, which has the side effect of making the audience like him (he doesn't intentionally kill the good guys anymore).
Also, it's been retconned that the real reason Brock decided to kill himself the night he bonded with the symbiote wasn't solely because Spidey ruined his career; it turns out Brock had terminal cancer, and the death of his career was just the final straw.
The recent Venom: Dark Origin keeps the lame motives, but brilliantly analyzes Eddie's past and shows that he is deeply mentally disturbed. And the ironic thing is, in real life, sometimes minor slights really are enough to make somebody your enemy.
Herr Starr from Preacher is an example of this as intentional character development. At first he is a Well-Intentioned Extremist, but after a series of unfortunate events that leave him mutilated, he becomes disaffected and gives up on his quest to better the world and merely seeks revenge. He openly states, after being told that he is a monster, that "Yes, I suppose I am. I became one a long time ago. At first in order to save the world. Now merely for the sake of vengeance."
Ironically, this may benefit the world anyway thanks to his actions leading to the complete and total collapse of the Grail, averting their world domination scheme.
Averted at the end of Final Crisis: Legion of 3 Worlds with Superboy Prime. He finally manages to get back home to Earth Prime but, at the end of the story, he wants to go back to the DC Universe(s). This is because Earth Prime is essentially our Earth, complete with DC books; Prime forgot that people can just pick up a book with him in it and see what a sociopath he is. As a result, everyone on his Earth knows he's a maniac, he lost his girlfriend (and either killed her or beat her up savagely), and his parents are dead fucking afraid of him; the reason he wants to go back is because at least in the Multiverse, Prime had superpowers.
He returns in a Blackest Night tie-in though still with his powers and he was able to regain some trust from his girlfriend (who was revived) and his parents. Or was he?
And then he returns in an arc of Teen Titans wanting nothing more than to kill Conner Kent again, for no reason other than he assumes Conner had something to do with dragging him back.
Spider-Manarchenemy the Green Goblin began his career as a ruthless businessman who sought to take over the criminal underworld, having already conquered the world of business. A number of failures at the hands of Spider-Man slowly downgraded his motives into ever more personal revenge on the spider, to the point where eventually Norman Osborn's entire life revolved around Spider-Man.
Though recently, he kept his eye on the ball and has taken over Fury's job.
Although even through that, he kept up the petty obsession with Spider-Man, he just had more resources to help him bear down on it. For instance, when working through his "List" of obstacles to take care of, he saved Spider-Man for last. Not because Spidey was any great threat (at least, no more so than any other individual hero), but because he wanted to give himself a "reward" for finishing the other items on the list.
His Ultimate Universe Counterpart is much the same. The man was originally only interested in patenting the Oz formula and making millions for replacing the Super Soldier Serum that created Captain America, but after his first arrest at the hands of Nick Fury and Spider-Man (and subsequent imprisonment) he started to shift his focus to revenge on Fury by destroying his career. After that was foiled enough times by Spider-Man, Norman changed gears again and focused everything on killing Peter.
The third Cheetah (and the most well-known of the Modern Age) who started out as a tomb raider greedily obsessed with mystical artifacts, hasn't mentioned them in about two decades, substituting that for just trying to kill Wonder Woman for whatever reason.
Giganta's motive, on her debut, was to escape her dying, pain-wracked body. She did that; since then, she's switched bodies again, and spends her time committing random criminal acts.
Circe, at least, started out trying to destroy Wonder Woman, but the specific reason why was resolved in 1991. Since then, exactly what she wants has been changeable and vague.
This is canon and justified for the Crucible in Knights of the Old Republic. The organization was created by one of the ancient Sith Lords to capture and train slave-soldiers for his armies, but by the time of the comics he's been dead and gone for centuries and the Crucible's only purpose for its crimes now is to perpetuate itself.
This has really become just a general result of supervillainy. Whatever reason the character was introduced, the self-perpetuating nature of the comics medium ultimately means that in order for the villain to put in a return appearance, they need a reason for him to be acting as a villain again. Once the original motive inevitably runs dry, many writers fall into the trap of "Supervillain A wants vengeance against Superhero B for defeating him the last 31 times he tried to complete his motivation!", which will be the character's new motivation for the rest of time.
The most cut-and-dried example of this variation in action is the vicious cycle of Doctor Doom and Reed Richards of the Fantastic Four. Doom originally had a murderous grudge against Reed because he blamed him for a botched experiment that scarred Doom's face, injured his pride, and got him expelled. However, every time he's tried to kill Reed or Take Over the World in order to get the power necessary to kill him, Reed manages to beat him, hurting Doom's pride even more because it proves Reed is still smarter than Doom, which makes him hate Reed even more, which causes him to redouble his efforts to kill Reed, which cause him to get defeated by Reed again, which hurts his already-injured pride even more, which makes him hate Reed even more... ad infinitum.
All Doom's Evil Plans suffer from this: no matter how coldly calculated and self-serving his manipulations are, and no matter how hard he tries to convince himself that he's doing it just to Take Over the World, they all eventually derail into an attempt to destroy Reed Richards' life.
Marvel villain The Hood originally had some sympathetic motives for becoming a supervillain, such as supporting his family. He gradually began to love the power his new hood and boots granted him more than he loved them. When he lost the hood and boots that allowed him to channel the power of Dormammu, he leaped at Loki's offer to repower him with the Nornstones. When he lost those powers almost as soon as he got them, he didn't take it very well. Then he went after the Infinity Gems. He seems to be addicted to power for its own sake.
Subverted by the Shocker, a charter member of Spider-Man's Rogues Gallery. All he really wants is to make a dishonest buck, and he otherwise doesn't really care about Spider-Man. The problem is that keeps running into Spider-Man over and over and over again every time he tries to commit a robbery or a hired killing...
Another subversion comes from the Beetle, an enemy of Spider-Man and the Human Torch. While he first sets out to get revenge on both of them, his defeats made the Beetle realize that revenge was a sucker's game and he resolved to only stick to straight crime. When the Kingpin's Arranger tried to hire him to kill Spidey, the Beetle flat-out refused... but the Arranger set up a situation where the Beetle ended up fighting Spidey anyway.
Despero, Justice League foe. When he first appeared he was a weird-looking alien despot, backed up by unseen tech that could teleport people and subdue them, fighting the heroes because they had accepted some refugees trying to overthrow him. But the more he gets used, the more power he gets and the less motive he has, so that as of just before Flashpoint he was a walking tank with telepathy, but apparently homeless and just battling the heroes because... revenge or something?
The Joker has his motives originally being a killer clown with almost no motive in his first appearances of the Golden Age, to just a common criminal after things like money in the Silver Age. However, it is averted nowadays, since his insanity means his reasons and motives to do anything can change at the drop of a hat. Most commonly they're a combination of It Amused Me and For the Evulz. That said, Joker's most consistent motivation for his actions involves screwing with and/or trying to kill Batman and his Batfamily in some manner or another.
Minor Batman villain Black Spider began as a high-tech vigilante who was targeting drug dealers. His origin revealed that he had been a junkie who had robbed a liquor store to score money for drugs, and killed the owner who turned out to be his father. After being arrested, he cleans himself up and declares war on the drug trade. At the end of his debut story, it was revealed the mysterious benefactor who supplied his high-tech weaponry was a drug lord who was using Black Spider to remove his competition. Later appearances tended to use Black Spider as a hitman, without any mention of his hatred of the drug trade.
Most Batman villains abandon their initial drive for an obsessive personal vendetta against Batman. In some stories, Batman actively encourages this, because keeping their hate focused on him means they're not going after innocent people.
The Mekon in Dan Dare originally wanted to conquer Earth for his scientific ends. The third time he encountered Dan, however, he appeared to be simply after revenge, with a plan to watch Dan die in an airless space capsule. In fact, however, he was subverting the trope because his main aim was the logical one of wanting to eliminate somebody who'd proved a threat to his plans. As soon as he thought Dan was dead, he set about trying to recover his lost powerbase on Venus. And in the next Mekon story, Dan returned to Earth to find that the Mekon had conquered it in his absence.
In The Transformers: More Than Meets the Eye it's shown that Megatron and the Decepticons originally started the war to overthrow the corrupt, evil Senate that ruled Cybertron and to bring an end to Functionism and bigotry against bots who were Constructed Cold. Over time the revolution slowly slipped beyond Megatron's original plans and he started to become Not So Different from the Senate, becoming convinced that the only way the galaxy would be at true peace would be if he ruled everything. By its end the Great War had pretty much devolved into the Autobots trying to keep the Decepticons from raping and pillaging the galaxy so they could rule it. Made even more clear by the fact that the Decepticons who stood against bigotry were massive bigots towards non-cybertronions.
Gargamel originally wanted to use one of The Smurfs as an ingredient to create the Philosopher's Stone and make gold. For some reason, in later seasons, he simply wanted to capture/eat/destroy them for no real reason other than they kept besting his last plan to get them. He got his original motive back in "A Child Among the Smurfs", but seemingly he forgets that he needed just one Smurf, and tries to get all of them anyways.
The Ultimates (2015): The team was initially founded with the aim of solving the "ultimate" problems, things on the scale of Galactus. Then Civil War II happens, and the team start serving as little more than, in Blue Marvel's words "a SWAT team" for Captain Marvel, who strongly disagrees, claiming they're still focusing on problems (America Chavez "disagrees" with that stance). Finally, at the end of the event the Black Panther publicly refuses to stand with Carol at all, outright telling her she'd ruined the team's initial purpose (absolutely no shade being cast on the team's portrayal in the event at all...)
Black Swan was introduced in Jonathan Hickman's Avengers as the last survivor of her universe, fully aware of the incursions that were destroying the multiverse. She took a strange view of events, seeing the event as the universe testing those who are worthy to survive, and was cryptic in regards to her goals. It's later revealed that her true goal was to find a universe where she could clone her family and be safe. To reach this goal, she aligned herself with whoever seemed like they might beat the incursions, until Secret Wars (2015), which resolved the incursions. After the story, and no longer being written exclusively by Jonathan Hickman, she appeared to still be working with Thanos when the Black Order try to claim the Ultimate Mjolnir, and later still is fighting alongside them in Avengers: No Surrender. Why she's still working with Thanos is never explained, nor are her motivations for doing pretty much anything aside from getting on with cloning her family (or even just returning home, since Reed Richards fixed the multiverse).