Sanji does this in the Thriller Bark arc of One Piece once he finds out an invisible man saw Nami bathing. Then he goes Super Saiyan.
Hogback pulls this after hearing that Luffy curbstomped Moria, though that may be anime exclusive
Sengoku literally pulls this after hearing that the Government wants to cover up the escape of countless dangerous wanted criminals from Impel Down
To some degree (a silent "what") this happened early on in the series a number of times when Luffy proclaimed that he will be the Pirate King someday. And more recently when Luffy said it straight to Whitebeard's face.
When Luffy uses Haki to knock people out (initially, without even knowing it)
In Higurashi No Naku Koro Ni's Meakashi arc, Shion lets out a rather unhinged one when Detective Ooishi informs her that Satoshi has "disappeared".
Meito Anizawa sometimes utters one of these whenever Konata bypasses something he's expecting her to buy.
Akira's response in the anime adaptation of Monochrome Factor when Shirogane cheerfully tells them that he's not longer human.
Bleach has Shinji and Hachi. The latter pulls a big "WHAAAATTTT?!?!" (or, in Japanese, "EEEHHHHHH?!?!"), and Shinji replies with "Don't 'WHAAAATTTT?!?!' me! You're standing there with your mouth open, looking like you're trying to catch flies!" (or, in Japanese, "Don't say 'EEEHHHHHH?!?!'! It's not cute when an old fart like you whines like that!")
In The Secret Agreement, Iori casually mentions in the middle of having sex that his wedding is the next day. "WHAAT!?" is probably the only response Yuuichi could articulate.
Annaka in Nichijou has her big "EEEEEEEEEEEEEEEEH?" that she does with regularity.
Katekyo Hitman Reborn! chapter 381 has Mukuro, Reborn, and Verde saying "What!?" in response to seeing what Vindice looks like without their cloaks and hats.
In 3-gatsu no Lion, Rei is a professional shogi player who keeps his status as one a secret from two of his friends, Hina and Momo. They react with an echoing "EEEEHHH" after finding out about this secret through an accident involving a taped video recording of one of his matches.
InuYasha has yelled this a few times. Memorable moments include one after being told by Kagome that she left their jewel shards in a demon-infested temple on the night of the new moon.
"My bag! I left it at the temple!"
"So get a new one."
"The things is… I left the jewel shards in it."
"Wh… WHAT'D YOU SAY?!"
In Turnabout Storm, Phoenix Wright collapses without warning in his office, and while he's paralyzed and unable to move or see, he hears an unfamiliar voice talking to him. Once he gathers the strenght to wake up, he sees the source of that voice.
Used in the Family GuyStar Wars parody, Something Something Something Dark Side, when Stewie declares that he is Chris' father.
Near the end of Harold And Maude, Maude tells Harold she took pills and will be dead in a matter of hours. There is a long pause from Harold before he says "WHAT?!".
At the beginning of Sanjuro, when Sanjuro finds out that the guy he pegged as the villain knows about the younger samurai's secret meeting place, he utters the Japanese equivalent: "NANIIIIIII?!"
A New Hope: Darth Vader does this when one of his TIE Fighter escorts is destroyed by Han Solo, preventing him from shooting Luke's X-Wing.
In A Christmas Story, Ralphie's mom asks him where he learned the word "fuck". He decides it's a bad idea to truthfully say his dad, so he says his friend. Ralphie's mom calls the friend's mom and notifies her. She screams "WHAAAAAAAAAAT?" and proceeds to beat the shit out of him without even hanging up.
In the first Underworld movie, Kraven does this when he finds out that "Selene's pet" (Michael) was bitten by a werewolf. His Big "WHAT?!" has the unfortunate side effect of waking up Viktor.
In Ali, this is Cassius Clay Sr.'s reaction when his namesake son informs him that he'll no longer be known by his father's name.
Elijah Mohammad:(to the man previously known as Cassius Clay, and later, Cassius X) From this day forward, you shall be known as Muhammad Ali.
(Cut to the next scene at the front yard of Cassius Sr.'s home, where a visibly shocked father turns around to face his son.)
Cassius Clay Sr.: What? You...you WHAT?!?
In the comedy Clean Slate, the hero lost his memory of his testimony for the mob, but taped what he could remember before he forgot the rest of it. Then he found his girlfriend accidentally taped over it, and did this trope.
Yellow Submarine: The Chief Blue Meanie after the Flying Glove misses at clobbering Old Fred:
Chief: What? What??WHAAAAT??! The glove is losing his touch!!
And before that, when Max says "yes":
Chief: WHAAAAT??! (lifts Max up by his ears) We Meanies only take "NO" for an answer!
Happens in King Kong after Ann and Jack escape the jungle and the crew prepares to leave the island.
Denham: Wait — what about Kong?
Jack: What about him?
Denham: We came here to make a moving picture, and we found something worth more than all the movies in the world!
Hercules: Hades does this twice:The first when Pain and Panic tell him he's late for his meeting with the Fates and again later, once he finds out that Hercules will stop his plans
Aladdin: Jafar uses this after Iago suggests he marry Princess Jasmine.
That reaction probably has more to do with the way in which he initially worded it, though:
Iago: Oh! Wait a minute! Wait a minute! Jafar? What if YOU were the chump husband?
Iago: Okay, okay, you marry the princess, all right? And... and uh, then you become the sultan!
Jafar: Marry the shrew? I become sultan? The idea has merit...
In still another Disney film, Cinderella, there's this exchange that takes place between the King and the Grand Duke after the ball ends and the Duke retrieves the glass slipper that Cinderella lost. The Duke has trouble getting a word in, because the King is ecstatic about the prospect of the prince marrying the beautiful woman who captured his heart. But when the Duke drops to his knees to explain himself and the King takes a sword and touches him with it to knight him, this little bit of dialog takes place:
King: I hereby dub you Sir... uh, hmm... Oh, by the way, what title would you like? Duke: Sire, she got away. King: Sir "She Got Away"? A peculiar title, but if that's what you— She WHAT?! Why, you... you traitor!! *uses sword to try and attack the Duke*
An episode of Babylon 5 had this when Londo and Lennier are involved in a brawl in the Zocalo. Sheridan hears about the fight and goes to his office. As the door closes, he hears who took ultimate responsibility for the fight (Lennier, to help Londo save face). Considering that Lennier is a Warrior Poet, his reaction is understandable.
One Kids In The Hall sketch featured a husband (Scott) who could apparently only say "What?"; as his wife (Bruce) kept looking at him without an answer while dusting, the husband quickly invoked this trope.
Vince McMahon: And next week, in spite of your insidious and stupid "What?"s— [WHAT?] Thank you. And, if you're an imbecile and you're from Hartford, you'll say— [WHAT?] That's my point.
CM Punk tried to do this when Vince Mcmahon apologized to him. However even after several invites the crowd didn't bite.
On I'm Sorry I Haven't a Clue, one of the rounds revolves around the panellists singing along to a record. The volume of the record is then turned down so that the panellist is singing solo. Points are awarded (allegedly) depending on how close the panellist is to the song when the record is turned back on, and whenever Barry Cryer gets the rhythm wrong (quite often), he tends to give a loud and shocked "What!?"
In Paper Mario: The Thousand Year Door, this is Professor Frankly's catchphrase. Usually given after the events of the last chapter were explained to him so he can act as Mr. Exposition for the next. It's delivered from outside his house in the form of a speech bubble that fills half the screen.
In Ace Attorney series, when the trials gets high-paced someone shouts it every couple of seconds.
Almaz from Disgaea 3 uses it multiple times, the biggest (And most hilarious) one being in the ending you get if he solos the last boss, where he's forced to become the overlord instead of Mao.
Used gratuitously in Dragon Ball Z: Burst Limit, 'WHAT!?' is the response from almost every character in the game, to almost every event that occurs in the game
Sam And Max Freelance Police: Sam does this in episode 205: "What's New, Beelzebub?" when they discover that Brady Culture likes Hell, but prefaces it with "Forgive me, my mouth is too parched for a Spit Take".
The last screen you see in Star Fox 64's ending is the team's bill to General Pepper for their services; do sufficiently well (i.e. score enough kills) and the sight of this prompts General Pepper to say "Wha?" in a tone of utter shock.
"An early preview" of Portal 2 used a placeholder voice actor (one of the programmers) for new sidekick character Wheatley, who added a particularly amusing emphasis on the phrase "You did WHAT?!"
In Kingdom Hearts II, this is how Sora, Donald, and Goofy react to two major revelations, both one after the other: first when they learn that Ansem, the Big Bad of the first game, was in fact the Heartless of a man posing as an entirely different character named Ansem; and again when they learn that the fake Ansem's Nobody is the current Big Bad.
They do it again (this time with backing from Riku, Mickey, and even Yen Sid) in KH3D in response to Lea nonchalantly summoning a Keyblade (and only giving a bemused "Oh" as a response) at the end of the game. Suffice to say, the collective fandom was pretty much doing the same.
Preceding the above Bison example, K' belts out a "Nandato!" as his K.O. cry in The King of Fighters XI.
Castlevania: Symphony of the Night features Alucard, who does this in gameplay a lot, when he's turned to stone, or untransforms in a tight passageway. For Dracula in the prologue, it's more like "big WHAT IS A MAN?!"
In Dawn of War 2: Retribution, it's one of the responses of Noise Marines to you clicking on them. Justified because they likely have trouble hearing you given that the majority of their weaponry is based entirely on the loudest, most discordant sounds that can possibly be produced by 40th millennium technology.
At the end of Dead Space 2 Nicole tells Isaac "Thank you Isaac. Now, time to die". He has just enough time to blurt out "WHAT?" before being pulled into a mental boss battle.
In Dragon Age II it's possible to get one out of Fenris by agreeing to give him back to Danarius.
Hawke (to Danarius): If you want him, he's yours.
Pokemon Mystery Dungeon: Gates to Infinity uses this trope A LOT!!! Even with the player himself. The player even lets out one after Hydreigon tells the player that Kyurem stands in Hydreigon's way of destroying the Bittercold.
Hydreigon: But there's something standing in my way. The one who stands guard over the Bittercold. Kyurem.
You (shocked): Wh... WHAAAT?! K-Kyurem?!
Flashback plays. At the end, it cuts back to the player and Hydreigon.
You: THAT Kyurem... is protecting the Bittercold?!
In an episode of Gargoyles, Lexington is trying to figure out where the sword Excalibur is hidden. The clan is in Manhattan, and Lex suddenly figures out "Brooklyn!". His clanmate with the exact same name, blurts out an annoyed, "WHAAAAT?!"
In Sponge Bob Square Pants, Plankton, disguised as Mr. Krabs, does this when attempting to get the Krabby Patty secret formula. He has to go through a tedious ritual, but Spongebob tells him that it's against the rules to tell anyone the formula. Bizarrely enough, this also doubles as a Flat "What."; Plankton's disguise is that of a robot with a very monotonous voice.
In South Park, Kyle's mom, when outraged, uses the catch phrase "What What WHAAAAT?"
And Ms. Crabtree, the cranky bus driver, will scream "WHAT DID YOU SAY?!" when one of the boys makes fun of her.
Meg: If you take him to jail, you have to take me too!
Joe: I know, that's the plan. You're under arrest for harboring an escaped convict.
Meg: Oh, well, that's only fair, because, after all, I did hide him from the WHAAAA?
Stewie's response to the announcement of a new baby brother in "Emission Impossible":
Stewie: A new baby? How wonderful. Call me when Kojak starts. (beat) WHAT?!?!
"Why, if we were all wiener dogs, our problems would be solved!" [PAUSE] "WHAAAAAAT????"
Two Pepe Le Pew Warner Brothers cartoons, 'Past Perfumance' and 'Who Scent You?', has this trope in the form of "Le What?!".
A funny example of this exists in an episode of The Dream Stone. One episode features the series main villain, Zordrak going to renew his evil powers, but on his way back to his lair, an incident occurs which results in him becoming good. Needless to say whilst he is in this good state and Urpgor tells him they have stolen the Dreamstone, Zordrak makes him return it 'with flowers and an apology'. A little later, a piece of rock falls on his head, and returns him to his normal state of mind. At the same time, Urpgor tells him that he returned the Dreamstone to the heroes. Which results in:
Another version occurs in the episode "Blob's Incredible Plan", when Zordrak finds out that Blob, Frizz and Nug stole Urpgor's Mole-Mobile:
Zordrak: They did WWWWWWWWWHHHHHHHAAAAAAAAAATTTTTTTTT????????!!!!!!!!
Played with in the third episode of Clone High. Donald Faison's character, a clone of George Washington Carver, is in a cop movie called Black & Tan with a clone of Gandhi, played by Michael McDonald. The script calls for Carver to recite the line "Say WHAAAT?!" This unfolds:
Carver:[flatly] Say what.
Gandhi: Cut! No, no, no, man! You're makin' me fall asleep! To death, bro! Okay, the line is: [high pitched, manner similar to Chris Tucker] "Say WHAAAT?!"
Carver:[flatly, again] Say what.
Gandhi: Say WHAAAT?!
Carver:[flatly, once again] Say what.
Gandhi: Say WHAAAT?!
Carver:Gandhi! This character is not me!
Gandhi: Say WHAAAT?!
Later in the episode, Carver converts it into "What is that you SAAAY?!"
Twilight Sparkle from My Little Pony: Friendship Is Magic has one of these near the end of Feeling Pinkie Keen, on finding out an attack by a hydra wasn't the "doozy" predicted by Pinkie Pie's "Pinkie Sense".
Twilight: Uh... but I... WHAT?! The hydra wasn't the doozy? How could it not be the doozy? What could be doozier than that?!
In "Sisterhooves Social", Rarity, Applejack, and Apple Bloom all let out Big Whats in quick succession when Sweetie Belle disowns Rarity as her sister in favor of Applejack.
Jake (pretending to be Finn):(after learning she's evil and psycho) Y'know, On Second Thought, we're not really each other's types... Flame Princess: ...We're... what? Jake (pretending to be Finn): I changed my mind. I don't like you. Flame Princess: You..... WHAT?!?!?!
Also Jake's reaction to the news that she's evil.
From Too Young:
Princess Bubblegum: Yo, EARL!
Princess Bubblegum: HEY- you're FIRED, 'ya BUTT!
In Jetsons: The Movie, George does this when his family asks him to close down the orbiting or asteroid plant. Bonus points for having it echo.
George: You want me to do WHAT??
Happens again a little later when George actually refuses an order from Mr. Spacely.
Spacely: Stay away from this button! That's an order!