Azula in the finale of Avatar: The Last Airbender . Her slippage began with Mai and Ty Lee's betrayals a couple episodes earlier. When Ozai told her to remain in the Fire Nation as Fire Lord, she became increasingly more paranoid. She acted on the paranoia, then began hallucinating, and eventually had a Villainous Breakdown.
Homer himself does so in The Shinning segment of "Treehouse of Horror V" when the cable stops working and they run out of beer, all thanks to Mr. Burns.
Homer: No TV and no beer make Homer something something... Marge: "Go crazy?" Homer: Don't mind if I do!! (proceeds to go crazy)
Toy Story. Buzz really doesn't take realizing he's a toy well.
Buzz Lightyear: YOU SEE THE HAT?! I AM MRS... NESBITT! (laughs maniacally)
Played for Laughs on Jimmy Two-Shoes, when Jimmy is left the only person in Miseryville awake while everyone else is in hibernation. He slowly begins to go crazy.
Sponge Bob Square Pants and Mr. Krabs try to keep their sanity when they believed they killed the health inspector. Turns out that the inspector is still alive, and the Krusty Krab passes inspection.
In "Pickles", SpongeBob's life takes a turn for the chaotic after a Jerk Ass customer claims that he forgot the titular condiment. By which we mean he tries to cook his bicycle and hangs the toaster on his front door.
Poor Squidward. In between being the entire ocean's Butt Monkey and victim to the constant shenanigans of his next door neighbors, SpongeBob and Patrick, it's no wonder he's been shown to break down into a sobbing wreck or fits of maniacal laughter when the Amusing Injuries and ever-present failures prove too much to handle. In "Squid's Day Off" Squidward tricks SpongeBob into running the Krusty Krab all by himself while he takes a day off, but he keeps imagining SpongeBob destroying the Krusty Krab and repeatedly goes back and forth to and from his house. While taking a bath he hallucinates SpongeBob is watching him and runs off to the Krusty Krab wearing only bubbles.
SpongeBob frequently has Sanity Slippage to the point that you wonder whether he's exactly sane to begin with...
(from "Stuck in the Wringer") Patrick: Hey, whatcha watchin'? SpongeBob:(watching static on TV) My favorite show. (the TV dies) Ha, ha, I love that part!
Mr. Krabs goes crazy when the squeaky noise of the rubber boots he gave Spongebob becomes too much to bear.
My Little Pony: Friendship Is Magic: The Fan Nickname for this is "Cutie Mark Failure Insanity Syndrome", given that a pony failing to live up to their special talent (symbolized by their cutie mark) is the most common cause of ponies going nuts. (It's worth pointing out that in all of these cases, the insanity was cleared up by the end of the episode with The Power of Friendship.)
In "Party of One", Pinkie Pie thinks her friends are avoiding her because they're sick of her parties. Her normally curly hair goes straight, she makes her own party guests out of things like a sack of flour and a pile of rocks (whom she holds conversations with), her colourful persona becomes noticeably darker, as if it's under a shadow, and the normally insufferably cheerful pony becomes cranky, miserable, and borderline paranoid schizophrenic, all the while sporting a Slasher Smile. Her slippage even comes complete with Creepy CircusMusic (which has a disturbing resemblance to the leitmotif of a certain personification of chaos).
Twilight goes crazy again in "It's About Time" due to a warning from her future self that got cut off before the important bit could be delivered, leading to a spiral down into the depths of paranoia.
Princess Luna experiences this a thousand years before the time of the series. Literally consumed with jealousy and anger towards the ponies rejecting her beautiful night in favour of Celestia's day, she transforms intoNightmare Moon and tries to enact eternal night in a stubborn attempt to force the ponies to love her, showing that even a Physical Goddess isn't immune to CMFIS. In "Luna Eclipsed" she runs the risk of having to bear these insecurities all over again when the ponies begin to reject her once more, but fortunately Twilight is there to help.
Before "Games Ponies Play" aired, people were expecting another "Twilight goes crazy" episode. They were likely surprised when this trope was averted for that episode because Cadance taught her a controlled breathing excercise to relieve stress.
But if her hyperventilating near the climax of the episode is anything to judge by, it was a pretty near miss.
In "Rarity Takes Manehattan", it's the title pony who ends up doing some hyperventilating during another of her epic freakouts.
In the King of the Hill episode "Pretty, Pretty Dresses" Bill is very lonely and depressed, and finally loses it when Hank destroys the gifts he'd been saving for his ex-wife Lenore in case she ever came back. He starts wearing her old clothes she'd left behind and talks in a falsetto voice, believing that he himself is Lenore; eventually Hank is able to break him out of it and gets him to get over Lenore.
In The Lion King 1 1/2, during a scene approximately taking place during Scar's Villain Song in the original movie, Timon is on the verge of cracking in his "dream home" quest...
Timon:(comes across a steam vent) Hey! This is home sweet home, baby! Home— (gets sent into the air a bit by the eruption) Ha ha! Steam! Ha ha! Steam is good. Steam is—is—is water. Whoo! Gotta have water. You know, for the dream home. Steam home, dream home! Steam, steam, steam.
The Christmas episode of Adventure Time shows that, centuries ago, before The End of the World as We Know It, this happened to an antique collector by the name of Simon Petrikov after he made the mistake of wearing a cursed artifact. A thousand years of sanity slippage later, the man he was is completely gone, and what remains only knows himself as The Ice King.
It gets worse. Later episodes document Simon's attempts at surviving and raising Marceline after the nuclear holocaust, and his desperation at remaining himself.
"But I'm losing myself and I'm afraid you're going to lose me too."
Looney Tunes: Daffy Duck seems to fall victim to this a lot. A perfect example occurs in Duck! Rabbit! Duck! after he gets shot by Elmer Fudd one too many times:
Daffy:(hysterical) Shoot me again! I enjoy it! I love the smell of burnt feathers! And gunpowder! And cordite! I'm an elk — shoot me! Go on, it's elk season! I'm a fiddler crab — why don't you shoot me?! It's fiddler crab season!
Meg Griffin from Family Guy quite frequently out of a desperation for love and affection.
Rugrats: From the movie, Tommy totally snaps and almost pours mashed bananas on Dil, knowing the monkeys will be attracted to it. It's thundering and raining the whole time, and Tommy just starts acting more and more crazy as he starts ranting about how much Dil has ruined his life.
Dib of Invader Zim isn't that stable to begin with (being one of the handful of reasonably intelligent people in a Crapsack Worldfull of idiots will do that), but over the course of the series becomes increasingly desperate, paranoid, and manic, and talks to himself with greater frequency.
While the Red Guy from Cow and Chicken isn't exactly sane to begin with, he ends up having a complete mental breakdown in the episode "I Scream, Man" as a result of taking a job that he despises: as an ice cream man. Predictably, he ends up in a mental clinic.
Red: AAAAAHHHH!!!!! I CAN'T TAKE IT ANYMORE!!!! I don't have any ice cream! Not one, so! EVER! (Hangs near the side of the cop, then switches to a calm, quiet voice) I don't even like ice cream, (switches back to Large Ham mode) OR KIDS! It says "Eye Screem" on my truck, not "Ice Cream"! Get it? 'cause I SCREAM!!! Look at me. (screams while spinning in circles) SCREAMING IS MY HOBBYYYYYY!!!!!!.
Policeman: (hits Red with a sausage) It's the padded cell for you, scream man!
Transformers Prime showcases Megatron's slow descent into (further) homicidal madness. Doping using the blood of Unicron certainly hasn't helped, but he's clearly slipping even without it. It becomes most clear when he get the Dark Star Saber, whereupon he starts shouting about how he'll tear this world apart (despite the fact that doing that dooms the entire universe).
Rigby of Regular Show goes cuckoo when he learns the "Death Punch of Death", to the point where he's willing to drown in lava if it means beating Mordecai at Punchie's.