There's also the never seen in-game character, Doug Rattmann, who has taken the time to write "the cake is a lie" at least 40 times in small dens throughout the game. Not to mention he covered the calendars' pictures of people with a companion cube.
Did we mention he apparently takes medication for his insanity and hears his Companion Cube speak to him?
Portal 2 almost has it worse. Including the Aperture Turrets from Portal, Portal 2 has a personality core that dispenses ridiculous ideas (justified in that he was created to be a moron), a for-real friendly turret that speaks nothing but seemingly nonsense, a CEO whose entire philosophy of science is to invent and then test bizarre things to see if they work or not without ever selling them (as well as making an entire speech about burning down life's house when it give you lemons), a core that talks constantly about space and going to space and his favourite part of space (which is space), a core devoted to ADVENTURE, and a core that spews random "facts" that range from being slightly correct to...not. A lot to deal with for just a single, silent sane character.
It should be noted that, being a Heroic Mime, we're only assuming that Chell is completely sane. Wheatley makes several comments about brain damage near the beginning of the game that actually do hold some water, despite his...quirk, as listed above.
In Touhou Imperishable Night, Reisen is the Only Sane Woman in Eientei among silly rabbits, lunatic princesses and Mad Scientists. Even more confusing because she is the Master of Lunacy.
Generally, it's quite probable that when the player character's personality and dialogue can be selected, and there are several party members with their own distinct and weird personalities, the aforementioned player character might be played as the Only Sane Man.
Haskill from Shivering Isles. Though the Shivering Isles is Sheogorath's realm, and Sheogorath is the Daedric Prince of Madness, being the only sane person there could make Haskill the maddest one of all...
Makoto is the same as Rachel. Apart from being a beastkin and a slight Bunny-Ears Lawyer, she's one of the few characters who could actually fit in real life.
Phoenix Wright of the Ace Attorney games counts as well. He appears to be the only (living) person in the courts able to put two and two together, meaning he often needs to explain in detail why such-and-such new point of evidence is important. While he enjoys this sometimes, he finds it very annoying when the Cloudcuckoolander judge fails to figure out obvious problems. In addition, he seems to be the only one to realize that the court system itself is insane and stacked against him. Similarly, he is often the only person who doesn't get swept away by some of the over-the-top personalities that he deals with, mostly because he's too busy thinking about how ridiculous these people are.
Apollo Justice counts even moreso.
This seems to be related to being an attorney, actually—Edgeworth seems quite sane, if you forget the whip thing Franziska's not bad, and Mia is reasonable when you play as her in Trials and Tribulations. The only really nutty one is Godot, who has his reasons for not being all there.
The fact that Edgeworth's "power" in Investigations is logic should say it all.
A lot of the relative insanity of the games, at least in the context of the court scenes, can be HandWaved by simply examining some of the more egregious examples. Typically, when the witness/accused/whoever is at the witness stand is trying to use their personality to sway the court, it works...for about three minutes until Phoenix or Mia or Apollo points out that they are wrong, at which point the judge rightfully asserts that the witness is not being truthful and it's much more difficult to sway him. In the cases where it works and sticks ( Furio Tigre, for example)), it's more because the prosecutor is all for beating up the defense attorney. In fact, despite the odds being stacked against Phoenix in every case he participates in, he always ends up finding the truth and getting his client out of trouble. Every. Single. Time. If the court system is stacked against him, he's certainly making good use of it.
It isn't until Apollo Justice figures it out by the time he is in his 3rd case. He realizes that despite the evidence he presented and the theories he gave, the court system will only accept hard proof, which is either definitive evidence or a confession from the killer, and Phoenix had to pull off the latter almost all the time, otherwise the case was lost. Not to mention that the burden of proof falls heavily on the defense while the prosecution can make an almost flimsy presentation and the court can accept it as truth because in the Ace Attorney world, "guilty until proven innocent," which is why Phoenix and Apollo have an extremely rough time trying to prove their case. And this is on top of the heavy penalties the defense can suffer from because the judge and prosecution want to see that the defense is giving solid proof and are not wasting everyone's time.
The first game's Penny Nicholz seems to be completely normal, barring her love of the Steel Samurai.
Common Nippon Ichi trope. Thursday and Etna comes closest in Disgaea: Hour of Darkness , Adell plays the role straight in Disgaea 2, as does Almaz in Disgaea 3 and Revya (and to a lesser degree Gig) in Soul Nomad & the World Eaters (Revya does not point it out, though obviously Gig does). Culotte from La Pucelle also qualifies (although Alouette is generally sane, Culotte is the one who usually has to deal with Prier's antics), and Pram is the closest you get to this trope in Makai Kingdom (which features an extremely eccentric cast, even by Nippon Ichi standards). This is not to say that Nippon Ichi games only possess insane people apart from these, but the only sane man is usually the one fated with having to present the sensible point of view to the more lunatic members of the cast.
Will/Ed during the War Room segments of Advance Wars: Day of Ruin due to being the only one who doesn't readily accept that the room ignores the world outside (thus allowing your current enemy to turn up to give tactical advise, or the War Room to show up in a mission on the wing of a giant plane).
Yuri Hyuga in Shadow Hearts laments the fact that he only ever seems to attract the strangest weirdos around in both allies and enemies. He overlooks the fact that, being a Harmonixer, he isn't so normal himself.
Johnny Garland, the protagonist in the third game, has the same problem. Even pointed out in one instance where he meets Mao, the talking cat that runs Al Capone's mob and specializes in drunken fist as he realizes that he is the only one out of the party who thinks that a talking cat is strange. This then makes Jonny wonder if he's the strange one.
Fable II has an odd example. Nobody in the entire world seems to notice that you are in possession of the ONLY DOG IN THE WORLD, except for a single demon door, who notes that he has never seen a creature like this in the multiple millennia through which he's lived.
You have the only domesticated dog. Wolves are everywhere.
Resident Evil has a huge cast of characters across more than a dozen games. Out of all of these, Linda from the second Outbreak game, is the only Umbrella scientist who isn't shown to be corrupt, insane, or a complete Jerkass.
Lupo from Resident Evil Operation Raccoon City is looking like this too. While her squad mostly consists of various sociopathic/psychopathic mercenaries with violent criminal pasts, the worst she ever did was kill her abusive husband to keep him from hitting the kids. The trailers still show her murdering RPD officers, though.
Yet it was amusingly subverted where he's not the Only Sane Man (ironically, Nikki played the role) when the party recruited a slug-like alien masquerading as an exchange student...
An Obviously Evil slug-like alien bent on world domination, no less. Nikki is the only one to notice the evil part, the world domination rants, etc.
And in the sequel, Mana Khemia 2: Fall of Alchemy, we have two examples: Raze in his workshop and Enna in Ulrika's workshop (or three, if Yun from the former's workshop also counts). At one point in the game, Lily even commented how staying in Ulrika's workshop for so long had ruined Enna, or something along that line.
Sarutobi Sasuke from Sengoku Basara. Pity him, for he has to put up with these two on a daily basis.
In Grand Theft Auto Vice City, the mock-public radio station hosts a debate program moderated by Maurice Chavez. Chavez is an egocentric fool, but he still nonetheless comes across as being reasonable and rational compared to the fanatical, deranged and downright insane guests he is forced to deal with.
Most of the GTA protagonists (three and after) fall into this category.
Mother 3 has its main characters, most especially Lucas. He is one of the few persons in all of Tazmily for the duration of the time skip who doesn't own a Happy Box and, more importantly, knows what kind of person Fassad is. (Of course, Flint doesn't either, but considering that he's been out every day for three years looking for Claus, he doesn't really qualifies as "sane" at that point).
Invoked with Squall Leonhart from Final Fantasy VIII, who is a character who thinks he is the Only Sane Man. Considering his past and his views on relationships with others, not to mention that he is surrounded by a rather quirky mixture of people, and it's not hard to see why he feels this way.
Sazh Katzroy from Final Fantasy XIII is very sane even if he does wear a chocobo on his head. He's just a civilian pilot dragged along with the vengeful, guilt-ridden, and actively delusional members of their little gang of the doomed.
In Dead Rising, most of the survivors of the zombie outbreak Frank encounters who aren't Too Dumb to Live turn out to either be up to something or completely insane. Two notable exceptions? First, Isabela Keyes, the sister of and co-conspirator with the Big Bad who, once confronted by Frank, cooperates with him and tries to reason with her brother only to be shot in the shoulder for it with him afterwards apologizing but encouraging her to carry on her part in their plan, not agreeing to cooperate with the protagonists whatsoever. Second, Thomas Hall, one of the three making up the trio-of-snipers miniboss fight - the other two are his father and brother, and a couple of Crazy Survivalists, but he actually seems pretty sane and is the only one of the three who objects to killing non-zombies, Some wonder why he doesn't do a Heel Face Turn if you kill the other snipers. Then again, killing the other snipers would probably itself be a good reason he wouldn't.
In Twisted Metal, if you win the Car Fu tournament, you are granted one wish by Calypso; however, Calypso is a Literal Genie, so most people who win get screwed over, either way. Agent Shepard, a character in Twisted Metal: Head-On, is Genre Savvy enough to outright refuse to wish for anything, and just arrest Calypso when he won.
In Two, Jamie Roberts is Genre Savvy enough to trick Calypso, allowing her to save her brother.
Lately, BioWare has made your starting male human party member the only really rational one of the bunch.
Alistair in Dragon Age: Origins is definitely the most well-adjusted of the group in a traditional human sense (though Wynne is pretty close on this one); Leliana and Zevran are both assassins who tend to use sex to get to their targets and both were betrayed by people they trusted implicitly with all of the issues that implies, Oghren is an exaggeration of the stereotypical drunk dwarf who was kicked out of polite dwarven society for a large number of reasons, Sten is from a very alien culture and has a tendency to solve many problems with violence, and Morrigan is a brutally pragmatic survivalist.
Jacob Taylor in Mass Effect 2 is a sane, well-adjusted, non-angsty man in a Ragtag Bunch of Misfitspar excellence and extreme Dysfunction Junction. The only other party member who comes close to his level-headed outlook is Tali, who has some hidden but deep-seated issues over the fact that for her people, Everything Trying to Kill You is almost literally the case.
Now now, don't be speciesist: Legion is perfectly sane for a Geth.
Except for a relatively minor and totally justifiable bit of anger-management trouble, Garrus is quite well-adjusted. He limits himself to sarcastic comments.
Thane is well-adjusted for a dying alien. Kasumi is well-grounded. Zaeed may be a sociopath but he's not nuts. Really, the only characters you may or may not team up with that might be considered not entirely there are Mordin (distracted mad scientist), Jack (homicidally pissed off experimental subject), Morinth (sociopathic sex-killer), and Liara (extreme guilt complex).
Quarian Admiral Zaal'Koris vas Qwib-Qwib is dismissed as a "geth apologist", who could easily be dismissed as either overly sentimental or even a coward for advocating against war with the geth, reasoning that the geth are the Quarian's children whom the Quarians themselves wronged. His position is largely disregarded or even ridiculed by his kin, who recognize the geth as the ones who rose up against them and cast them off of their own homeworld and forced them to live on a fleet of cobbled-together ships with a degraded immune system. He's right: the geth hold no animosity toward their creators, went to war only in self defense and if the Quarians asked nicely, the geth would almost certainly let them back onto their home planet; moreover, besides being unnecessary, war with the geth would certainly divert resources from both sides that would be better directed toward the Reapers. He ends up fully vindicated in Mass Effect 3..
Varric and Aveline switch off here in Dragon Age II, Aveline during most of the game and Varric near the end. Nobody else is remotely well-adjusted.
In World of Warcraft Jaina Proudmoore has to take this role for the vast majority of Alliance/Horde interactions, since she's apparently the only one to have truly grasped the concept that when your quarrel with one group comes down to history and cultural differences less extensive than exist within your own faction, while your opposition to the other is based on them wanting to wipe out all life, stop fighting the first group for five minutes.
Jaina tends to view herself as the Only Sane Man, but given that the group she so adamantly protected from her allies just destroyed her home city Theramore, it seems she was just a Wide-Eyed Idealist while Varian was Properly Paranoid.
Venus Jones of Space Colony, one of the few crew members without serious mental issues.
Vindictus has Shayla as the closest thing to a sane person (the player character doesn't really count). She's essentially the only one who fully realizes and admits what is actually going on with the Fomor Wars, and how thorougly messed up the situation is. All of the other NPCs are far too obsessed with politics and religion (the Royal Guard and Crimson Blade Mercenaries particularly), behind-the-scenes conspiracies ( Brynn and Nyle), and/or personal issues (Kirstie especially, but just about everyone else as well); when they're not simply drunk (Fergus). That doesn't stop her from profiteering and otherwise using the situation to her advantage, however; making her a clear Type 3.
The protagonist of Persona 4 leans towards this in his dialogue options, especially since one of the most common options for him in "Calm down." Comes to a head when the party is fighting over what to do with Namatame and the correct sequences of options leads to "Calm the hell down!".
Colonel James Hsu in Fallout New Vegas is the only one of the NCR top military brass in the region that seems to have his head on straight. Colonel Moore and General Oliver are both jingos and have a delusion that the NCR is invincible. Oliver has the added problem of being a General Failure trying extremely ineptly to walk into the history books over the bodies of hundreds of NCR troops. Ranger Chief Hanlon, while he may share Hsu's opinion that the NCR's in quite a predicament in the region, decides to solve the various problems by covertly sabotaging the NCR's efforts.
Veronica is the only member of the Mojave chapter of the Brotherhood of Steel who is willing to make an effort to change their xenophobic and isolationist ways, which she sees as the group basically committing slow suicide. While Elder Nolan McNamara does have similar sentiments, he's both too afraid of the NCR and unwilling to break the Brotherhood Codex/commit outright heresy. Depending on how her personal quest ends, Veronica will either stay with the Brotherhood in order to help her family or try to join the Followers of the Apocalypse. Either choices sees her being attacked by fanatical Brotherhood Paladins for not being homicidally zealous enough.
The Courier becomes this in the Old World Blues DLC due to being stuck in a World of Ham research facility with various Mad Scientists, a base full of dysfunctional sentient home appliances who all hate each other, and a very long string of previous visitors, all of whom were lobotomised into drooling, ax-wielding maniacs.
Dr. Moebius also has shades of this, as he realizes the extreme danger that his colleagues' reckless science would have on the rest of the world. Unfortunately, he is mitigated by drug-induced senility.
Gene from God Hand qualifies as well, noting the unusual antics and oddities of the world as all other people seem to simply ignore them. Among these oddities, a succubus fleeing battle in a teleporting bus, a Monkey Luchadore, who turns out to be a man in a costume, and his epic line "You're all a bunch of freaking idiots!" when his longstanding enemies flee from him after being defeated.
General Knoxx, leader of the Crimson Lance in Borderlands: The Secret Armory of General Knoxx is pretty much the only sane man in the Crimson Lance. The rank-and-file seem more concerned with ice-cream than their mission, the elites are Ax Crazy (they were brainwashed as children then forced to murder their parents) and his boss is a freaking toddler. All while trapped on a desert planet loaded with crazies and vicious alien wildlife. He's so fed up with the situation that when the Vault Hunters find him, he's trying to kill himself to escape the madness.
Similarly, in Borderlands 2 you have Roland, one of the P Cs from the first game, building a sanctuary city, rallying a resistance, and worrying about organization and infrastructure while two of the other P Cs literally lead or inspire cults of madmen, the fourth spends his time sniping anything that moves while drunk with his pet bird, the _computer narrator_ is a compulsive liar, and the main villain spends as much time shopping for diamond-plated horses and hiring you to kill yourself as he does actually trying to maintain his hold on the planet.
And don't get me started on Scooter and Moxxi. Imagine them, but about 100 of them in two clans.
Kenji and Hisao both claim they're this in Katawa Shoujo. Kenji is quite offended at Hisao's claim: "There can't be two last sane men . . . There can only be one, like in that foreign movie where there could only be one, and in the end there is only one dude left, because that was the point." (In other words, Hisao is, Kenji only thinks he is.)
Emily in Deadly Premonition, who is the only other character besides York who wasn't born and raised in Greenvale, and really has no other quirks or eccentricities that the entire rest of the cast has.
In Bully, Lance Jackson is the only member of Bullsworth who isn't a bigot, a social malcontent or mean to others.
In Shin Megami Tensei as a whole, the only two members of the Celestial Paragons And Archangels who are not completely obsessed with The Evils of Free Will and hopelessly devoted to the will of YHVH are the Archangel Gabriel and Remiel. Remiel, particularly, gets a lot of flak from other angels for being so damn devoted to this "strange, impossible idea" of salvation for all, not just some of the Chosen, up to and including people who are generally considered irredeemable. Gabriel, while still very much a Knight Templar, distinguishes herself from the other three classical Archangels (Uriel, Michael and Raphael) for being significantly more interested in the quality of human life and generally having a firmer grasp on the Smart Ball.
Clank in Ratchet And Clank All 4 One; at one point Qwark considers using the area they're in as a vacation spot, Nefarious tries to cajole Ratchet into letting him kill Qwark, with Ratchet considering. Clank has his hands full trying to keep the group together.
Most of the Characters from Team Fortress 2 suffer from some form of severe mental illness, But as shown through the comics, the Spy seems to be the only member of either team who will actually plan in advance or think about what’s going on. Maybe all that nicotine helps him keep a clear head.
Don't forget about the sniper.
The Engineer is always, and we do mean always, shown to be calm and level headed, with only a couple lines of dialogue displaying any form of anger. According to this psychoanalysis, the Engineer truly is the only sane man, his only problems being "minor paranoia, coupled with some perfectionism", neither of which is actually canon.
The protagonist is the only one in Dra Koi who seems to actually be at all well balanced. His classmates are all crazy and his mother wants to rape him. The dragon herself indicate she'd like to eat him or sleep with him and sees little difference between the two options.