In Terrydacty Land in Tooie, some of the dinosaurs and Mesozoic reptiles are done like realistic dinosaurs, so this trope comes to mind when the cartoony-looking Banjo and Kazooie are seen next to one. Best example would be Chompasaurus, the plesiosaur that eats you.
Beautiful Grunty from the first game's Game Over cutscene.
As fantastical as the designs are, the angels of the Bayonetta franchise usually follow a similar design formula ... until you get to the Irenic from the first game. They were added last minute to a Unexpected Gameplay Change driving section when the developers realized the level had no enemies, and they are designed to look like a classic car, with an angelic marble face on its grill and Holy Halos for wheels. They apparently were created from taking a very liberal artistic license with the concept of the Thrones/Ophanim angels, which were described as chariots of Heaven, although they are given a Hand Wave in-story as being given credit for inspiring humanity to enter the Industrial Revolution when they took a joyride on Earth a couple centuries ago.
Isaac's Mom from The Binding of Isaac, in-gamenote Cutscenes draw her like any other character. The rest of the game uses a simple, oddly "cutesy" (despite the graphic violence and Body Horror) way to depict Isaac and the enemies. Mom, however, appears in Gross-Up Close-Up, from her overweight leg when fought in battle to the image of her shirtless when using her bra as an item.
While most of Borderlands is done in a Thick-Line Animation style, The Guardian Angel is portrayed as an FMV of a real woman whose image appears on the top of the screen whenever she communicates with the player. In the sequel, this is revealed to be due to the fact that she is a Siren interfaced with all technology on Pandora. Near the endgame, when Angel dies and Lilith is kidnapped to replace her, Lilith communicates with the player in much the same way.
The Professor, his pet dog (who thinks it's a cat) Mochi, and his spaceship in Contact are in a Retraux pixel art style that's vastly different from everything else in the game.
The few females with above small breasts (the Nekomata, Succubus, and Jennifer) are significantly different looking because they were drawn by a different character designer (who did designs for earlier Nippon Ichi games).
Kurtis is significantly different looking from the other characters, his design being based heavily on Jet Link. The Prinny commentary in the DS version makes a point of repeatedly mocking his nose.
Asagi was originally from Makai Kingdom before she started making appearances in the Disgaea series, so she had slightly different proportions than the rest of the cast. But this trope really came into play in Disgaea 4, where every character gets nice looking HD sprites... and Asagi's still pixilated! If you speak to her, a few of her quotes draw attention to this fact. A high-res version of her is free DLC, however. And the new Asagi will even talk about how nice it feels to be HD.
Both Usalia and Christo differ from the rest of the characters in their design — namely, their ears. Usalia is the only character in the main cast to not have pointed ears on the side of her head, which is a trait she inherited from her parents, both of whom had rabbit ears (daddy's a literal rabbit). Christo also has pointed ears on his head, which wouldn't be noteworthy if you exclude the fact that he's an angel, and thus should have a rounded pair like the rest.
The second Fossil Fighters game, Fossil Fighters Champions, underwent an Art Shift from the first game, and features a more anime-like style when compared to the first game's cartoony visuals. Those few characters who do appear in both games (like the dinaurians) feature updated looks to fit the new style... with the exception of former sidekick Rosie, who retains the first game's heavily cartoony style.
Hero & Daughter is a RPG Maker game mostly made with the assets from that program, but the portraits of the girls the hero can recruit are pastel-colored original designs, drawn with fairly simple shapes and curved lines. The difference with the semi-realistic anime style of the rest of the game is quite noticeable.
Horizon Zero Dawn uses it as a subtle foreshadowing, where the Corruptors and Deathbringers look far more alien and manufactured than the other machines, which all look like robotic wildlife. That's because unlike the other machines, they are relics of the old world from before the apocalypse.
Jones in the Fast Lane: Most characters in the game are digitized photographs. The computer-controlled opponent Jones, however, is a highly cartoonish, big-headed fellow, which is quite jarring.
Kid Icarus: Uprising has Magnus, an old(er), muscled, bearded, deep-voiced, dark-clothed, BFS user. He completely (and intentionally) clashes with the rest of the game's aesthetic by looking noticeably less stylized (and by being the Anti!Pit in design).
In Birth by Sleep, instead of getting a design in Nomura's normal style but with bigger feet and brighter colors, which is standard for the Final Fantasy cameos, Zack Fair's design is heavily influenced by the style used in Hercules, while still retaining a Final Fantasy style face and hair.
In Dream Drop Distance, characters from The World Ends with You show up. They're not that out of place, but like the Zack example above, their extremely thin style, carried over from their home game looks a bit odd compared to the still stylized, but not to that extreme, Sora and Riku.
Similar to the example above, Last Scenario is also a RPG Maker game created mostly with assets from the program. The character portraits, most of the enemy sprites and cutscenes images all follow the same art style. Some of the monsters such as wolves, kobolds and elementals, in the other hand, were taken from the stock graphics of the program and they kind of stand out like a sore thumb among the more subdued and realistic art predominant in the game.
In The Legend of Zelda: Breath of the Wild, the Mooks and field bosses have fairly whimsical designs, with even the more realistic-looking Yiga Clan still being humans with somewhat goofy bodily proportions. The exceptions to this rule for enemies are the Blight Ganons, dungeon bosses which are Mechanical Abominations made up of gruesome mixes of Malice and ancient Sheikah Magitek with no legs, misshapen arms, and freaky-looking cybernetic "faces." Calamity Ganon itself is an especially large and grotesque entity designed along this same theme, with its face in particular consisting of a mechanical skull-like mockery of Ganondorf's original human face.
In Mass Effect2 and 3, Tali'Zorah is the only quarian with her form of unique suit design (with the head cloth attached to her shoulders and wrapping around her waist). The rest of the female quarians have a simple cloth hanging like long hair, and all male quarians look the same except for suit colors.
By Mega Man 6, the bosses have become more detailed (tricks are used to keep the same colors), while the hero still has the simplistic design he had in the first game. Once the series got off the NES, though, everyone got new sprites, and this was no longer the case.
The fourth game of the Mega Man X series has Colonel's younger sister Iris, who is drawn more Moe than the Shonen-y style than everyone else shown.
It's not as if characters based off real actors is uncommon in the Metal Gear world, but the BB Corps in Metal Gear Solid 4: Guns of the Patriots took it one creepy step further by being digitally-scanned-in Serkis Folk, instead of completely digitally rendered like everyone else. While they look quite pretty on their own, if you don't look too closely, there's enough of a subtle anime influence to the faces of the rest of the cast that the proportions look subtly off in comparison, and their eyes in particular look completely dead. They'd all undergone heavy Mind Rape and were no longer either physically or psychologically entirely human, so this was very, very intentional.
Due to its Loads and Loads of Characters, multiple authors, and accessibility, it's not uncommon to see a couple (or even 3 or 4) characters in a M.U.G.E.N fight that look NOTHING alike. They can also end up on a stage that suits none of them.
While most of the champions in Paladins have semi-stylized designs, Moji stands out by having a small, cartoony design that makes her look like she's from another game, like Gigantic.
Natu and Xatu have very unusual eyes compared to most other Pokemon, which is said in-universe to be the result of them being able to see the future.
In Pokémon Black and White, one of the gym leaders, Cilan, is a polite young man with green hair and... Skintone Sclerae, making him the first character in the entire franchise to have these. It looks rather creepy compared to everyone else.◊ In the anime series based on the Black and White games, a number of original characters were created, one-shot and recurring, that had the same eye style as Cilan's, who was a traveling companion during that point in time, making the design choice not stand out as much.
The Ultra Beasts in Pokémon Sun and Moon look insectoid, alien, and completely unlike any other Pokémon (whom, incidentally, they're at first outright considered to be completely separate beings from), and look more like strands of DNA. Of course, that they look like they come from another universe entirely is fitting because... well, they do.
Also from Sun and Moon is the legendary Pokémon Necrozma, a pitch-black crystalline being who looks otherworldly even compared to the Ultra Beasts.
Hapu from Sun and Moon resembles a young child, but doesn't quite look like the other children in the game, nor does she even act like one. Her proportions are different.
During post-game content for Sun and Moon and Pokémon Ultra Sun and Ultra Moon the player can defend their title as Champion against a rotating set of potential challengers. Most such challengers are characters encountered during the rest of the games' story. The lone exception is Ryuki, a dragon-themed musician who has a much sharper and more aggressive-looking character design. It's somewhat justified in-universe as Ryuki explains that he's come from another region of the Pokemon world outside of Alola (though which one is never specified).
Project X Zone: While every character has dozens of highly-detailed sprites, the characters from Gods Eater Burst have certain attacks involving their transforming weapons animated frame-by-frame, making them look incongruously fluid and profoundly out of place.
Rouge the Bat is an anomaly in the otherwise noodle-limbed character designs in the series, since she has a much more anthropomorphic figure, complete with human-like breasts and legs suggesting actual anatomy.
While most of characters are based on animals and follow a strict design style, the Deadly Six from Sonic Lost World are instead based on demons (specifically Youkai), and look very out of place. Justified by the fact they are native to a different planet.
In a world of anthropomorphic sea animals, Judd the cat stands out as the only land mammal. He's actually Really 700 Years Old over thousands of years old. He was frozen before humans became extinct and is thus the only surviving land animal.
Moe is the only character who is neither a Funny Animal or humanoid. Instead he's a talking clownfish.
While the Inklings' hair come in a variety of different colors, the Squid Sisters and their grandfather Cap'n Cuttlefish are the only ones with unique colors. Callie is black, Marie is white, and Cap'n Cuttlefish is gray. However, Super Mario Maker shows that Callie and Marie's squid forms are colored in their signature clothing colors (pink and green), rather than their actual hair colors, unlike other Inklings.
The Squid Sisters once stood out as the only Inklings with unique hairstyles. In Splatoon 2 the Inklings clearly have a variety of hairstyles as opposed to having the single ones defining sexual dimorphism, making it no longer be the case.
Pearl from Splatoon 2 is the only adult Inkling with only one pointy tooth. Prepubescent Inklings are the only ones previously shown to have that trait.
Spooky's Jump Scare Mansion: Spooky herself and most forms of Specimen 1 are in a limited and cute-looking art style. This is to trick unaware players in to believing that this is what most of the game looks like, but after being introduced to the various actual horrors inside, Spooky quickly ends up becoming outnumbered and has the odd design out. It's even more apparent when you compare the Cute Ghost Girl design of Spooky to Specimen 4, a Stringy-Haired Ghost Girl.
In Super Mario RPG, Bonus Boss Culex is designed more like a Final Fantasy enemy than a Mario one, including having a static 2D battle sprite instead of animated faux-3D like the rest of the game.
Those realistic-looking grubs found in the "Gusty Garden Galaxy" level from Super Mario Galaxy (which can be used by Mario/Luigi as ladders to get from one planet to another there). They totally clash with the series' art style especially when there are already Wigglers (cartoony grublike enemies that debuted in Super Mario World which get angry when Mario/Luigi stomp on them) found in that game.
On the subject of Paper Mario, in Super Paper Mario, many of the new characters and enemies (as well as the latest iteration of the Merlon family) are made up of geometric shapes and stylized in general, while the returning cast and enemies (as well as the Koopa Striker family of enemies) keep the same design aesthetics established in the previous games of the series.
On the subject of the Paper Mario series, most characters are depicted as paper-thin 3D models, rather than sprites. There are, however, several bosses that break this trend and use full 3D models, which becomes more common within the series until Super Paper Mario has all of its bosses doing this. This began in Paper Mario 64 with the Koopa Bros' Bowser??? Tank and General Guy's lightbulb tank. The first game also had the elder tree in Flower Fields which is depicted more as a talking landmark than a normal character model.
As well as the New Donk City residents, who are realistic looking humans that look somewhat bizarre next to the cartoony Mario ones.
The various kingdoms feature a realistic Shiba Inu that Mario plays with.
The Sand Kingdom has a realistic steppe eagle that Mario has to hit in order to gain a Power Moon.
The frogs in the Cap Kingdom are also realistic.
Some of the background animals (lizards, squirrels, pigeons, doves, bats, gulls, crabs, and various fish) are realistically proportioned compared to the others.
Finally, there's also the Ruined Kingdom in general, which features a boss called the Ruined Dragon, a.k.a. the Lord of Lightning. It looks like it came straight out of Dark Souls or The Elder Scrolls V: Skyrim.
Mario Kart 8 goes out of its way to avoid this with Guest Fighter Link. Though based on the Skyward Sword incarnation of Link (Or the Breath of the Wild one, in a later update for the Switch version) Link's design is simplified and he's given proportions in line with Rosalina or Waluigi, to fit the Mario series cartoony aesthetic.
In Ultimate, the tradition of basing the non-Toon Link version of Link and other Zelda characters was eschewed in favor of incorporating different character designs from different games. As such, the roster includes Link from Breath of the Wild, Zelda from A Link Between Worldsnote Justified, since her BotW version was more of a researcher than a warrior princess, Toon Link, Ganondorf from Ocarina of Time, and Young Link from the Nintendo 64 titles.
In a world full of pixellated sprites, Photoshop Flowey's "realistic" appearance emphasizes its otherworldly and godlike nature and serves to make the various disgusting details of its design even worse.
There is also Burgerpants, the neurotic, despairing Burger Fool employee, who seems to have been designed with John Kricfalusi's "go Off-Model every time, run rampant!" philosophy, and thus ends up with some pretty out there facial expressions.
Sans and Papyrus, who are both skeletons, have dialogue that resemble their respective font types.
In Warframe, the eponymous Warframes normally lack facial features, which just makes it all the more unsettling that all of Mirage's helmets feature eye-like lights on them.
In Witch's Wish, most of the town inhabitants look much cartoonier compared to Vicky and other main characters, who are drawn in an anime style.
Xenoblade Chronicles 2: All of the game's rare blade characters were designed by guest artists, and as a result some of them have very different styles. Vess is probably the clearest example, being drawn in a mid-90's anime style as opposed to the more modern styles that most of the other blades use. Another example is The Architect, whose design is far more detailed and realistic-looking than the more Animesque style of the rest of the game.
Yo-Kai Watch: Most humanized yokai are cartoonish looking. But then you have characters like Lord Enma, Zazel, and especially Kaira (a Half-Human Hybrid) who just look like standard humans with minor differences.
Inhert, with its gel armor on a visible skeleton and goddess statue on its cockpitnote which is located on the head as opposed to the crotch of other orbital frames, and Lloyd with his three rods sticking out of his head, are all rather different from the other Zone of the Enders mechs and characters. This is due to being designed by Kazuma Kaneko instead of Yoji Shinkawa.