In Kick-Ass Damon's old police partner, Marcus Williams qualifies as this. He's the only one to point out to Damon that his plan of he and Mindy dressing up in costumes and carrying out vigilante justice is insane.
Dave also has a moment of this, but doesn't give up being Kick-Ass though.
In horror scifi thriller Sunshine, Chris Evans' character Mace is the only guy who seems to have common sense and an idea of the bigger picture. Makes you wonder why he wasn't captain instead.
Star Wars: General Cassio Tagge at the Death Star military briefing.
Planet of the Apes. George Taylor has the only rational response to a world where apes rule over men.
Ironic in that it was Chapman who frequently played the zaniest Cloudcuckoolanders in the series.
Chapman has also been cited as the funniest of the Pythons by the others, although hampered by alcoholism. He was certainly the edgiest: his writing contributions to the series are easily discernible by their being markedly more unpleasant, mean-spirited and of general poorer taste then the others (a notorious example being the undertaker sketch where Chapman's undertaker is suggesting they eat the corpse of Terry Jones' dead mother, "and if you feel guilty later we can dig a grave and you can throw up in it"). One theory as to why series 4 was so much nastier than the first three is that John Cleese - Chapman's traditional writing partner and moderating influence - had left the group.
In the Death sketch in Monty Python's The Meaning of Life, the Grim Reaper gets this role. He comes in to claim the souls of a bunch of people in a dinner party but it takes five minutes for them to understand that he's not there to reap the hedge, doesn't want wine and won't discuss philosophical topics with them.
Robert: He knows the song too? I've never heard this song before! What the hell is it?!
Arsenic and Old Lace (1944), with Cary Grant as Mortimer Brewster, the token Only Sane Man surrounded by his rather... quirky family. Insanity can be contagious, if only because we as humans derive our idea what is sane from the people around us.
Unusual in that it is one of the very few examples in which the rest of the characters are, in fact, completely mad, and not just irrational, carried away, or mind controlled.
Nicholas Angel in Hot Fuzz, surrounded by a lazy police force who don't take any of his suspicions seriously.
Shaun of the Dead: Nobody, with the possible exception of Yvonne, begins as this—they can't even comprehend the idea that the dead are rising up and trying to eat them, and fall back on pretending there's nothing wrong. However, Shaun evolves into this when he finally decides to fight back. Of course, 'sane' is relative as his plan to hide in a pub gets most of them killed (the other survivors we see flee in the opposite direction and do much better).
In I, Robot, when Doctor Calvin calls Detective Spooner insane after he shoots a (blank and mindless) robot in the face, he replies "Does thinking you're the last sane man in the world make you crazy? Because if it does, then maybe I am."
Mittens the cat, in regards to Bolt and Rhino, in Bolt. "How do you say 'There is no way I'm doing this!' in Crazy?!"
An incredibly depressing one in HBO's Conspiracy, which is a dramatization of the real life Wannsee Conference (when the details of the Final Solution are worked out and the various relevant individuals notified) comes in the form of Dr Kritzinger. He tries to make a moral stand (everyone else is concerned with bureaucracy or power-play), and is shot down and eventually goes along with it. It is summed up by this exchange at the end of the film:
Kritzinger: It is night in Moscow already. Soon it will be dark here. Do you think any of us will live to see the daytime?
General Hoffmann: Come spring we will be on the move again. Keep your spirits up.
Mr. Furious: That's because Lance Hunt is Captain Amazing. Blue Raja: Oh, here we go. Shoveler: Oh, don't start that again! Lance Hunt wears glasses. Captain Amazing doesn't wear glasses. Mr. Furious: [Long-suffering] He takes them off when he transforms. Shoveler: That doesn't make any sense. He wouldn't be able to see!
Colin Powell, in the movie W.
Part of Mugatu's Motive Rant / Villainous Breakdown in Zoolander is his claim that all of Derek's looks are identical. (See the quote on the works page.) This is enough to spur Derek into creating a new look that involves turning left instead of turning right, which has the power to stop a shuriken in mid-air and even Mugatu thinks that it's beautiful.
Even then, the new look is a mirror reflection of all his others.
Subverted by Truman in The Truman Show as he slowly figures out that he is living in an artificial world; of course, the other actors are already aware of it, so they try to disabuse him of the notion when he explains his concerns to those around him.
Buck in Uncle Buck, especially during the second half.
A famous example is Zeppo Marx from the Marx Brothers films. In a group of comedians with defined by distinct comedic styles (The comedy of Groucho, Harpo and Chico came from wit, slapstick and double-entendres, respectively), Zeppo was defined only by his lack of a "quirk". His roles were the definition of a straight man.
... though interestingly, all of the Marx Brothers and many of their colleagues are on record as saying that in real life, Zeppo was easily the funniest of the brothers, and certainly the only one to be able to reduce Groucho to tears of laughter. Zeppo even stood in for Groucho on-stage when Groucho was ill, but didn't like performing and left the act as soon as he could. Fifth brother Gummo admitted he was no performer, and only ever appeared on-stage a few times, and never on film... his non-status in the family act was such that he volunteered to be drafted into the army so that none of the other brothers would be forced to join too...
The Bridge on the River Kwai ends with Major Clipton looking around at the carnage and destruction surrounding him, and declaring, "Madness! Madness!"
Tropic Thunder: Kevin Sandusky and to a lesser extent Alpa Chino spend much of the film trying to rein in their unhinged costars. Their success is limited.
Kevin Sandusky: Tugg. Tugger. You're the last piece of the puzzle buddy. We need you! Your men need you. Are you with us?
Tugg Speedman: [pause] I'm a rooster illusion.
Kevin Sandusky: Fuck it. We'll deal with him later.
Kirk Lazarus has flashes of sanity, usually to contrast with Tugg. As a general rule within the film though, the sanest person in any room will be the one with the lowest status. (For instance, Kevin is most sane because he's the least famous actor.)
Laurie and her school newspaper staff in The Wave, among the few students who are trying to stand up to the quasi-fascism sweeping their school.
Jaws: Matt Hooper tells Chief Brody that he will be "the only rational man left on [Amity] island" after Hooper leaves the next day to join a shark research vessel.
Ted in Burn After Reading. A former man of the cloth, he now works at the Hardbodies gym. He is practically the only normal character in the entire film, which is filled with delusional characters who are mostly Too Dumb to Live. Ted nurses an unrequited crush on his colleague Linda, and she is blissfully oblivious to his quiet affection. At the end of the film, it's revealed that Ted was shot and killed. With a hatchet.
The CIA director as well.
In Dagon the only sane man is the town drunk. Uh-oh...
Played with in What About Bob?? At first Dr. Marvin is the only one who sees anything wrong with Bob's obsessive, manipulative, stalker-ish behavior. Bob becomes better socialized and more acceptably-quirky over time. Dr. Marvin tries to kill him as revenge for earning his family's appreciation.
Duncan, sort of, in Mystery Team. Although still maintaining his childish personality, he is slowly revealed to be more and more normal than we are led to believe.
Chef in Apocalypse Now was described by Captain Willard as being "wrapped too tight for Vietnam; probably wrapped too tight for New Orleans."
In El Arca, everyone seems to be totally in love with the female panther Panty, all of them singing and dancing to her song "I will Survive", none of them seeming to notice she's talking about MURDERING AND EATING THEM except for the pig, who is clearly uneasy and suspicious, while everyone else, including the other prey animals, is completely oblivious to the actual words of the song, only really seeming to pay attention to Panty's...um...''assets''
Smith in Sleeping Dogs attempts to stay aloof as civil war breaks out, but is caught up with it despite his best efforts. He spends the rest of the film vainly trying to escape the madness, without success, until the end where he seems to bitterly accept his fate at which point he gets killed.
Peggy in The Woman is the only one who really criticizes her father Chris' idea of trying to "civilize" the feral woman he captured, what with her mom Belle being too henpecked to stand up to him, her brother Brian being too much like his dad, and her little sister Darlin' being too young and naive to know any better. She's also the only member of the family, other than Darlin', to survive to the end.
Alan is this in American Dreamer, due to "Rebecca's" antics even getting the police to believe her over him.
Agent Coulson in The Avengers. Fury is busy trying to control and lead the Avengers around by their noses, Steve is blindly obedient to Fury for the first half of the movie and wrapped up in fighting with Tony and Thor, Natasha is openly disdainful of and uncommunicative with the rest of the group, Thor is preoccupied with Loki and a Fish out of Water, Tony is flippant, abrasive, and always at SHIELD's throat, Bruce is paranoid and suspicious of everyone, Clint is a brainwashed minion, and everyone is constantly bickering. In the end, Coulson is the only one who has it together enough to think ahead and head off Loki's escape attempt with a special BFG cannibalized from Asgardian tech, and understand that the Avengers need something in common to fight for before they can be of use. His subsequent murder, which was partly the Avengers' fault (as they were too busy arguing to catch the ambush Loki's minions launched on the Helicarrier before it happened), causes everyone to go into Let's Get Dangerous mode pretty quickly, and Steve takes over the Only Sane Man position.
In WALL•E, Captain McCrea is the only human on board the Axiom that isn't entranced by the 700-year-long ennui of their existence.
Corporal Joe Bowers in the 2006 Mike Judge cult comedy Idiocracy, who having been stuck in suspended animation for over 500 years while humankind has grown progressively stupider and stupider, awakens as unquestionably the smartest man in the world. Alas, Joe's notably superior intelligence is often for vain when dealing with the dunces in this idiotic dystopia, which is played for laughs throughout various situations at Joe's expense. At one point, Joe asks members of the President's cabinet why plants are being watered with a Gatorade-type sports drink, Brawndo; their only response is to repeat Brawndo's advertising slogans over and over to him ad nausem. Even when compared to his only other current-day contemporary, Rita (a former prostitute), Joe comes off as clearly more sensible (given that Rita is convinced her former pimp could travel through time to find her.)
The first mate in Ghost Ship. After Santos is killed and they're stranded on the Graza, Greer is the only one to really show concern that the ship might be haunted, and that they should forget the gold, forget salvaging the ship, and get off immediately. This makes his subsequent fall into deadly idiocy rather out of character.
Ed Du Bois is probably the only logical and sane character in Pain and Gain. All others do stupid errors, none moreso than our protagonists.
In the 1966 flick King of Hearts Private Charles Plumpick was literally the only sane man in the French town of Marville, due to it having been evacuated by the regular citizenry before being repopulated by escaped denizens of the local insane asylum.