* NolanNorth, the voice of [[{{Uncharted}} Nathan Drake]] and [[Franchise/AssassinsCreed Desmond Miles]], plays [[FatBastard The Penguin]] in ''VideoGame/BatmanArkhamCity''.
** He also voices [[ThoseWackyNazis Edward]] [[MadDoctor Richtofen]] in NaziZombies.
** He lent a vaguely nasal voice to the [[HeroicComedicSociopath hilariously insane]] Steven Heck in ''VideoGame/AlphaProtocol''.
** His role as Captain Walker in ''VideoGame/SpecOpsTheLine'' [[PlayingWithCharacterType starts out]] as a slightly more serious version of his typical role (Drake voice included) only to gradually morph into [[ShellShockedVeteran something]] [[NeverMyFault entirely]] [[HeWhoFightsMonsters different]] over the course of the game.
** He's also the voice behind ''SlyCooper 4'''s El Jefe.
** He also stars in ''VideoGame/TransformersWarForCybertron'' and its sequel, ''VideoGame/TransformersFallOfCybertron'', as Brawl and Bruticus, the resident Decepticon [[TheBrute brutes]]. In ''Fall of Cybertron'', it's further highlighted by his more in-type role as Cliffjumper.
** Not to mention Deadpool in ''VideoGame/MarvelVsCapcom3'', one of his highest-pitched and least serious roles he's ever had.
* RobPaulsen as Gray Fox in the remake ''VideoGame/MetalGearSolidTheTwinSnakes''. 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.
* Creator/AdamBaldwin departs from his earlier psychotic roles to voice the polite, respectable, and intelligent ([[ObfuscatingStupidity though he insists otherwise]]) Quarian marine Kal'Reegar in ''VideoGame/MassEffect2''.
** Meanwhile, respected actor MartinSheen normally plays fatherly type figures, mentors or moral leaders. Not so in the ''MassEffect'' series where he voices [[TheChessmaster the head of the pro-human terrorist organization]], Cerberus and the universe's resident MagnificentBastard, [[KnightTemplar The Illusive Man]].
** Also, SteveBlum, who's damn near unrecognizable as Grunt or [[spoiler:the Shadow Broker]].
* [[Series/StarTrekVoyager Kate]] [[TheCaptain Mulgrew]] as [[VideoGame/DragonAgeOrigins Flemeth]].
* MauriceLaMarche voices Calendar Man, a murderer who commits his crimes on certain holidays, in ''VideoGame/BatmanArkhamCity''. Normally, he plays comedic roles.
** He also plays [[AntiVillain Mr.]] [[WoobieDestroyerOfWorlds Freeze]] in the same game, a character who is definitely not a comedic role.
* SpikeSpencer plays Arakune in ''VideoGame/BlazBlue''. He normally plays small and cowardly boys. Instead, here he plays a psychotic blob monster with a [[EvilSoundsDeep much deeper voice]] than what he's used to.
** In ''VideoGame/FireEmblemAwakening'', he voices Excellus, a [[SissyVillain Sissy]] SmugSnake [[DudeLooksLikeALady who Looks Like a Lady.]] Seriously.
** ''VideoGame/BlazBlue'' is one huge testimony of TetsuyaKakihara Playing Against Type. The man who was known for his young, sometimes naive, but undeniably heroic roles like [[Anime/TengenToppaGurrenLagann Simon]] or [[VideoGame/TalesOfHearts Shing Meteoryte]] gets landed in the role of Jin Kisaragi, arrogant {{Jerkass}} extraordinaire, practically a KnightInShiningArmor GoneHorriblyWrong. If that wasn't enough, [[spoiler: Tetsuya Kakihara also voices Jin's future self, Hakumen, who speaks in a deep and slightly mechanical voice, and a ''booming'' LargeHam at that!]]
* CharlieAdler plays Super-Skrull in ''VideoGame/MarvelVsCapcom3''. While he's played Super-Skrull in some of the villain's animated appearances, he's way better known for playing small FunnyAnimal characters than intergalactic warlords.
* ChristopherLee voicing DIZ in ''KingdomHeartsII'' qualifies as a PlayingAgainstType, as the guy usually plays villainous roles, and yet in this game, he's actually a hero. [[AntiHero Kind of.]]
* CharlesMartinet, who is best known for playing [[SuperMarioBros Mario]], plays TheMentor Paarthurnax in ''[[VideoGame/TheElderScrollsVSkyrim Skyrim]]'', one of the most [[TheAtoner complex]] and [[CainAndAbel compelling]] characters in the history of the Elder Scrolls, not to mention someone who talks a lot, that alone is a huge contrast to Mario.
* Creator/JoshKeaton is well known as the voice of many a teenaged hero, such as SpiderMan. Then along comes ''NoMoreHeroes'', where he lends his voice to the AxCrazy superhero-themed assassin Destroyman.
* AliHillis voices mainly stern, serious no-nonsense characters such as [[VideoGame/FinalFantasyXIII Lightning Farron]], [[MassEffect Liara T'Soni]] and [[NinjaGaiden Mizuki Mccloud]]. Then there's [[KidIcarusUprising Palutena]], who is anything but.
* Aaron Spann is well known for voicing good boys like [[VideoGame/DissidiaFinalFantasy Onion Knight]]. Then there comes [[VideoGame/TheWorldEndsWithYou Joshua]], where he lends his voice to an [[SmallNameBigEgo arrogant]] [[InsufferableGenius genius]] [[SmugSmiler smiler]].
* Danny Jacobs is probably best known for being a PoorMansSubstitute of SachaBaronCohen as [[Film/EpicMovie Borat]] and [[WesternAnimation/ThePenguinsOfMadagascar King Julien]]. In ''VideoGame/BatmanArkhamAsylum'' and its sequel, ''VideoGame/BatmanArkhamCity'', he lends his voice to the creepy, knife-wielding psychopath Victor Zsasz.
* LiamOBrien is normally known for playing either outright villainous or [[AntiHero Anti-Heroic]] roles. In ''VideoGame/FireEmblemAwakening'', he voices a purely-heroic, not-angsty-in-the-slightest ChivalrousPervert who's [[ShrinkingViolet secretly a bit shy.]]
** And a far cry from the brooding, contemplative characters he tends to voice, he's Asura in ''VideoGame/AsurasWrath''. Still brooding and contemplative to an extent...but with a lot more HotBlooded screaming.