Mulan II derails several characters: in addition to giving Mushu Aesop Amnesia and making him a bigger jerk, Mulan and Shang start arguing using sex stereotypes as insults, and Chien Po goes from a Gentle Giant who loves to eat to a flat Fat Comic Relief character who is Obsessed with Food (and engages in pointless brawls, something he pointedly did not do in the first movie). But the character who got it worst was Ling, whose personality got traded in for... wanting someone to laugh at his terrible jokes. This becomes his motivation despite not even being hinted at in the first movie.
Titan A.E. manages to derail a character within one film. When Korso is revealed to be a Drej agent, the charismatic and competent captain of the Valkyrie is replaced with a bullheaded brute who makes rash decisions and is outwardly antagonistic towards Gune and Stith. Even when he makes a HeelFace Turn, it's still such a drastic change in character that you wonder why Gune and Stith hadn't cottoned on sooner.
Considering all of its faults, many agree that one of the greater atrocities committed by The Secret of NIMH 2 was entirely derailing the character of Brutus; changing him from a white-eyed, silent, spike-wielding gatekeeper into...a blundering, idiotic side-kick to the also-somewhat-derailed Justin.
The original book Mrs. Frisby and the Rats of NIMH did actually reveal Brutus to be a pleasant guy just playing the shadowy guard act to scare away intruders. Similar to the Aunt Shrew example, it is more the fault of both films for not elaborating on this enough.
Or Auntie Shrew scolding Martin for badmouthing Nicodemous and insisting that he was a great oracle or something - despite the fact that she clearly was shown in the first movie distrusting the rats (though it's possible she thought better of them after they helped the Brisby family, there really isn't any mention of this).
Halloween: The Curse of Michael Myers: Michael Myers was known as an iconic soulless killing machine who can't be intimidated, bargained with, reasoned with, or stopped, and whose only explicit motive was to kill his family. In the director's cut of this movie, he rapes and impregnates his niece on someone else's orders.
Dr. Lawrence Gordon's long-awaited return in the series counts as this. This is considering the last time we saw him (in part 1), Lawrence was crawling away from his bathroom-prison, shivering from the blood-loss incurred from cutting off his foot and promising he'd find help for the still-shackled guy being tested with him (this is after he believes his family may well have been shot and killed due to his inaction in the "test"). In Saw 3D, he is a willing accomplice to John "Jigsaw" Kramer. In the first scene we see Dr. Gordon in during the present-timeline, he is delivering a cheesily villanous sounding monologue to the protagonist of the film, his smirking henchman demeanor majorly contrasting with the distrought husband/father he had become throughout the first film. Whatever real change occurred apparently happened completely offscreen, and what's more, apparently happened in the span of about two months, as we see Dr. Gordon smiling whilst placing a key behind a trap-victim-to-be's eye during a flashback that slightly predated part 2. At no point in Saw 3D does he mention his family or the guy he left behind, and ends up only looking at the latter's corpse rather dully during the climax when he returns to the bathroom.
An even better example is Jigsaw himself. Jigsaw made a huge point that he never killed anyone, merely put them in position where they had to fight and occasionally compete to live. Then in Saw VI he suddenly was fine with using Hoffman's traps, which did kill people outright.
They didn't kill people outright any more than Amanda's trap in the very first film did, or Gordon's test as intended. Come Saw 3D he has no real such excuse, as the final trap is impossible and kills Joyce out of spite rather than as a result of Bobby's own failure. Add this on top of the aforementioned Gordon example, Jill's severe Chickification, and Hoffman's Flanderization into an Ax-Crazy slasher villain, and everyone got derailed in this movie.
It's worth remembering that Jigsaw did mortally wound a police officer with a concealed dagger during the first film, and there was no way that innocent man just doing his job could have "earned" his survival from that attack. His moral stance can seem more of a pretense for his actions rather than a motive when you take that into account.
Purposely done in the case of Susan Orleans in Adaptation.. Portrayed as simply a reporter who develops a bond with John Laroche, due to Charlie Kaufman's in-story Creator Breakdown she proceeds to become a psychotic drug-addict who regrets her life.
Space Jam does this to Bugs Bunny. Usually, he's a laid-back, sarcastic, mischievous Karmic Trickster who'll stand up to anybody - no matter how much bigger they are - if they antagonize him and is always able to outsmart them. In Space Jam, meanwhile, he's a pathetic loser who's actually afraid of, and outsmarted by, a group of tiny dimwitted aliens and needs the help of the other Looney Tunes characters and Michael Jordan to defeat them. Even when Bugs was afraid of his opponent in the original shorts, he would never beg another character for help. Not only that, but at one point he actually needs to be saved from a dog. That's how pathetic Bugs is in this movie.
Unfortunately, Falcor also got this treatment in the third movie. He was initially a wise, gentle creature that would gladly lend a helping hand, but in this one, he's the dragon equivalent of Scooby-Doo.
Michael Corleone. Compare this character between of The Godfather Part III and the rest of the series. In the first two parts he was a dead-serious and moody fellow. In the final sequel he's got cute quirks and snarks.
Heisei Rider Vs Showa Rider Kamen Rider Wars Featuring Super Sentai is an infamous example among Toku fans. Unlike most "Versus" movies, this isn't a fake-out; the Showa Riders have a major quarrel with their juniors, attacking them while Badan raises a literal Army of the Dead. And even after Badan is defeated, they still insist on fighting the Heisei Riders. What's their beef with the younger heroes, you may ask? The fact that they remember and honor their deceased friends. Ignoring the fact that this makes the Showa Riders look heartlessnote or how it makes them look stupid; the Heisei Riders' attachments to their dead friends helped Badan bring back dead enemies, but they didn't bother explaining this until after Badan was defeated, instead jumping straight into attacking the Heisei Riders, it completely ignores the fact that practically EVERY Kamen Rider has lost a friend or family member somewhere along the line (creator Shotaro Ishinomori envisioned them as "crying heroes"). The Derailment actually bothered Hiroshi Fujioka (the star of the original Kamen Rider, who returned in Heisei vs. Showa) so much that he ended up co-writing his own movie to do justice to his character.
Original solicitations for the film suggested that there was a different conflict: the Showa Riders prioritized defeating evil, while the Heisei Riders prioritized protecting the innocent, as seen with their helping a young boy say goodbye to the spirit of his dead mother. While this is still Derailment (since Kamen Riders are all about protecting humanity's peace and freedom), it's not nearly as bad as what we got in the final movie.