Mad Eye

If a character is deranged, or has just lost it for a moment, they are depicted as having one eye much larger than the other. Can also double as an unspoken Oh Crap moment. For extra effect, may be paired with Twitchy Eye.

Not to be confused with a certain former auror.

Examples of Mad Eye include:

Anime and Manga

Just about everyone in the Hellsing manga.
Solf J. Kimblee in a late chapter of Fullmetal Alchemist. He's telling Pride about how screams are soothing to him...
A favorite shot of Magical Girl Lyrical Nanoha's resident Mad Scientist, Jail Scaglietti, when he's taunting the Time-Space Administration Bureau via broadcast.
Higurashi no Naku Koro ni has a lot of "emo-distortion" expressions, Mad Eye being just one of the effects. Rika busting this out in the second season is truly a sight to behold.
Kurt Godel from Mahou Sensei Negima (possible spoilers)
Marik of Yu-Gi-Oh! did this from time to time, though he was crazy all the time, and this was because it was his dark side.
- In Yu-Gi-Oh! R, Yako Tenma has this going on at least once in just about every one of his appearances after his Start of Darkness. He's not quite right in the head, in case you couldn't tell.
The entire cast of Deadman Wonderland exhibits this, sometimes as their default expression. It fits, since most of them are clinically insane to some degree.
Ryuga does this quite often in Metal Fight Beyblade. It succeeds in making him appear quite off his rocker (and he is).
86 from Vassalord has this as his default expression. And when 86 gets serious somehow his eyes get even more crazy looking!

Comic Books

Johnny the Homicidal Maniac. Quite a lot of the time, really. But then, he's insane quite a lot of the time.
And on that note, pretty much anything by Jhonen Vasquez has this.
The Mask: link
Falling under the "Deranged Character" subset are The Joker's eyes as drawn in Batman: RIP. There, one of his pupils is drawn slightly larger than the other, giving him a dangerous and mentally off-kilter look. The effect is so slight that it's only noticeable in close-up shots of the character, but it's definitely there. Then again, he is a Complete Monster Clown with enough crazy to fill Arkham Asylum's halls ten times over.

Film

In 9, 6 has one eye slightly larger than the other as a permanent feature, confirming his Cloudcuckoolander status.
In The New Guy, Luther teaches Dizzy his "Crazy Eye" which consists of squinting one eye and opening the other wide.

Literature

The aptly-named Mad-Eye Moody from Harry Potter.
The unnamed old man in Edgar Allan Poe's classic The Tell-Tale Heart. One eye, due to some deformity, is permanently open with a film over it. However, the eye drives the old man's roommate to insanity (whether this roommate is his servant, his apprentice, a caretaker or even his spouse is never mentioned).
The Scarecrow from The Wonderful Wizard of Oz is described as having one eye larger than the other (accompanied by mismatched ears) due to poor artistry on his creator's part. He never really loses his cool at any point in the book, and he is never depicted as any more crazy than the rest of the Ozians, so it might be considered Subverted.

Mythology

Having a literal Mad Eye is Older Than Print: Cuchulain, the Irish folk hero. Whenever he went into one of his unstoppable rages, one of his eyes would get smaller and the other would get bigger. " ... he sucked one eye so deep into his head that a wild crane couldn't probe it onto his cheek out of the depths of his skull; the other eye fell out along his cheek." Now thats a Mad Eye.

New Media

This guy: o_O

Newspaper Comics

Bill the Cat from Bloom County.
Cartoonist Steve Bell depicted Tony Blair with an increasingly mad eye.

Tabletop Games

One Paranoia mission has a General Ripper who "glares at his subject with one bulging and one squinting eye: paranoid fear and clinical suspicion".

Theme Parks

The Ghost Galaxy in Space Mountain: Ghost Galaxy has one skeletal-eye-socket and one giant blue nebula-eye.

Video Games

King K. Rool from the Donkey Kong game series.
Earthworm Jim: Jim himself.
In the re-render of Kingdom Hearts: Chain of Memories, Vexen gains one of these.
Laverne from Day of the Tentacle has one eye bigger than the other permanently. Which one depends on what side of her head you're looking at.
Similarly, Doug Rattmann from the Portal games has one pupil permanently larger than the other. He's also a paranoid schizophrenic.
Whenever Glottis from Grim Fandango gets excited about cars, or customizing something else with a motor or wheels, or gambling, he goes crazy-eyed, rapidly switching from one side to the other.
In the Creepy and Cute pack for Spore, one of the added emotes (for the creepy side of things) is a version of this. Hilarity Ensues when your creature is covered entirely in eyes.
In Nintendo World Cup, characters would get this when stunned by a tackle.

Webcomics

Black Mage, from Eight Bit Theater does this a lot, and was stuck for a while after a particular bit of frustration. As he put it after listening to one of Red Mage's "plans", "That's so stupid I can't even see straight."
The titular amorph from Schlock Mercenary has one eye that is literally larger than the other, and the cartoonist is consistent about which is which, and what side each is on. Since Schlock can move his eyes around it doesn't really matter though.
The Monster in the Dark from Order of the Stick, though no more than anyone else in the comic.
Several characters in Girl Genius do this sometimes... and there's one, a construct, who really does have one eye bigger than the other.
Bob from Bob the Angry Flower. When Bob's scorching feral mania comes to the fore, he gets the Mad Eye.
Vatsy, the insane journalist from Vatsy and Bruno, is always drawn with one eye in shadow to accentuate his wrong-ness.
Helen Narbon of Narbonic gets this occasionally.
Kano of Kagerou is frequently seen with pupils of very different sizes, though his actual eyes are the same size. The effect is halfway between Mad Eye and Mismatched Eyes.
Nova from Keychain of Creation, especially when in Mad Scientist mode.

Web Original

The eponymous character from Spoilsbury Toast Boy has this permanently, as does his sister.
Bubs, from Homestar Runner, definitely looks like this, but is no more crazy than the rest of the cast.
Zero Punctuation will sometimes show these, usually of the Oh Crap variety, having a character with one eye as a ring and the other as a circle.

Western Animation

Bumi from Avatar: The Last Airbender.
Many characters from Invader Zim, including the titular invader on occasion.
Mr. Demartino from Daria.
Blitzwing from Transformers Animated has asymmetric eyes in one of his three faces. He's definitely crazy, having three personalities and all, but the odd-sized are on the most calm and calculating face. Really, it's mostly there to make it look like a monocle, as an Homage to Colonel Klink.
Shado the Brain Thief from Harvey Birdman, Attorney at Law. His mad eye alternates from right to left.
Uncle Ruckus in The Boondocks.
The Tick (animation)—the title character, who is never entirely straight.
Vince from Rex the Runt, one of the more random oddballs in claymation: given to random fits of Pavarotti and tangential one-word sentences.
The starring spider in the (still unfinished) Art Institute of Portland student production Tangled Web, sometimes. Then again, he's decided to become a vegetarian and is desperate to avoid the delicious, delicious fly that's just landed in his web, so can you really blame him?
In An American Tail: Fievel Goes West, Wiley Burp teaches Tiger how to intimidate someone using "The Laaaayyyyzzzzyyy Eyyyyye!" which is essentially an intentional ecovation of this trope.
The Vigar puppet on Brats of the Lost Nebula was the first one with different sized eyes to be approved by Brian Henson.
VERY evident on Ed, Edd 'n' Eddy. "Boy Double D. Eddy never stares at ME like that."
In The Critic, Duke Phillips once answered a reporter's question by telling him to "stare deep into the hypnotic powers of my EEEeeevil eeeye!" It apparently works.
Discord of My Little Pony Friendship Is Magic has Red eyes with two irises of different sizes to illustrate his... discord!
- More commonly used on the show as a brief, unspoken Oh Crap moment on the part of main cast.