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.
The Little Mermaid II: Return to the Sea, which is very ironic, considering the title character becomes a parent! The first movie shows Ariel as being curious, open-minded, brave, and impulsive. The sequel gave Ariel a horrible case of Aesop Amnesia, causing her to make the exact same mistakes with Melody that Triton did with her. And that's not even counting the very stupid decision to keep Melody's heritage and background a secret from her, arguably giving her better reasons to be defiant than Ariel, who at least knew why her father had the rules he did.
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 Heel–Face 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.
It should be noted that 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).
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.
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.
Norrington in the Pirates of the Caribbean movies. In the first one, he is Will's rival for Elizabeth's affections and, as a naval officer, hates pirates and is out to get Will and Jack. But he's far from a bad guy, takes it gracefully when Elizabeth chooses Will over him, and gives Jack a Mercy Lead at the end. When he comes back in the second movie, suddenly he's a bitter drunk with a grudge against Will for getting the girl and Jack for escaping and ruining his career, and he becomes a pirate himself. The third movie tries to reconcile these two portrayals and treats him a bit better, but Redemption Equals Death and he gets killed off rather abruptly.
This didn't go entirely unnoticed in the second film, however; he mentioned that the reason he lost his career and went drunk was because he lost his ship and got his entire crew killed in a hurricane he only got caught in because of the Mercy Lead from the first film. Survivor's Guilt was heavily implied.
Michael Corleone. Compare this character between part III of The Godfather 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.
Jim Phelps in the first Mission: Impossible. Fans of the TV series were not happy when he turned out to be a traitor who sold out his own team leading to almost all of their deaths. Peter Graves even refused to reprise his role because he felt that it completely betrayed Phelps' character.
The entirety of "Heisei Rider Vs Showa Rider Kamen Rider Wars Featuring Super Sentai" is one long Character Derailment of the Showa kamen Riders (ichigo through J), as their actions in that film are not only hypocritical, but vastly out-of-character for individuals who condemn their juniors for events they themselves have gone through and struggled to move past. Specifically lingering connections to the dead through their memories of them, as EVERY PROTAGONIST KAMEN RIDER has lost someone significant to them. It gets so bad in the movie, the legacy heroes of the franchise act little better than the monsters they charge themselves with facing.
This is because the writer of the Taisen films knows little to nothing about characters he himself did not create, has been cited as doing this as Far back as Post Staff change "Kamen Rider Hibiki", and does it in pretty much every film for this franchise he has written.