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- Nolan North, the voice of Nathan Drake and Desmond Miles, plays The Penguin in Batman: Arkham City.
- Rob Paulsen as Gray Fox in the remake Metal Gear Solid The Twin Snakes. Basically, the fact that Rob Paulsen played a very serious character (a character who is implied to be driven insane from experimentation as well as at times remorseful of his past in war, and in one source was implied to have PTSD) and do so in-character is a very sharp turn against some of his more lighthearted and comical roles.
- Daran Norris is known for playing goofy characters such as Cosmo and Timmy's Father. He also plays Rodyle from Tales Of Symphonia, a rather frightening mad scientist.
- Adam Baldwin departs from his earlier psychotic roles to voice the respectable and intelligent (though he insists otherwise) Quarian marine Kal'Reegar in Mass Effect 2.
- Kate Mulgrew as Flemeth. Seriously. Kate Mulgrew as Flemeth.
- Maurice LaMarche as Calendar Man in Batman: Arkham City a Hannibal Lector esq sadistic murderer who commits his sprees on holidays. Normally, he plays comedic roles. (Incidentally, Calendar Man isn't normally a sadistic killer.)
- He also plays Mr. Freeze in the same game, a character who is definitely not a comedic role.
- Spike Spencer plays Arakune in Blaz Blue. He normally plays small and cowardly boys. Instead, here he plays a psychotic blob monster with a much deeper voice than what he's used to.
- Blaz Blue is one huge testimony of Tetsuya Kakihara Playing Against Type. The man who was known for his young, sometimes naive, but undeniably heroic roles like Simon or Shing Meteoryte gets landed in the role of Jin Kisaragi, arrogant Jerkass extraordinaire, practically a Knight in Shining Armor Gone Horribly Wrong. If that wasn't enough, Tetsuya Kakihara also voices Jin's future self, Hakumen, who speaks in a deep and slightly mechanical voice, and a booming Large Ham at that!
- Charlie Adler plays Super-Skrull in Marvel vs. Capcom 3. While he's played Super-Skrull in some of the villain's animated appearances, he's way better known for playing small Funny Animal characters than intergalactic warlords.
- Kevin Michael Richardson portrays Chairman Drek in Ratchet and Clank, even though he usually portrays characters that are large or at least tall. Of course, Clank is one of the eponymous heroes and he also has a voice deeper than his appearance would suggest.
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