The one time Artyom speaks in Metro 2033 is when he yells "guhhh-fffFUCK" when he notices that a derailed train is about to crush him into the ground.
The Metal Gear series is very low on swearing, so the one F-bomb in Metal Gear Solid 4 is a laser-guided Precision F Strike indeed. Delivered by what turns out to be a mind raped psychopathic teenage girl who never stopped her deranged laughing for years, "It's all so FUCKING HYSTERICAL!!!" manages to creep you like you wouldn't believe.
Especially considering the creepy nature of the boss fight, against an enemy who uses stealth against you. Cue the nightmares.
In the Japanese release of Metal Gear Solid 3, EVA, when cornered by Colonel Volgin, snarled 'fuck you' before trying to shoot at him with a concealed gun. In the English version, the line was changed to the more mild 'go to hell' - although it was saved by the voice actress's delivery.
In Mega Man 7, Bass throws in a rather unexpected "damn" in a dialogue toward the end of Shade Man's stage. Mild by the standards of a T-rated game, but it was quite surprising in a KA-rated SNES game. Too bad it was taken out in the Anniversary Collection.
Mega Man X had a couple "damn"s in the early games, which were kept in the X Collection. Although the fourth game missed its chance by having a late boss character shout, "See you in the underworld!" rather than the less unwieldy "See You in Hell!"
In the X Collection, one "damn" (from X no less) was actually added for some reason.
Mega Man Battle Network 2 also has one, when, after you defeat MagnetMan, and expose Gauss as the hijacker, he lets out a rather unexpected "Damn it to hell!"
MMBN2 had several other times incidences as well, unlike the rest of the series. Oh, and the guy wasn't hijacking the plane, he was trying to crash it.
Example using mild swears: despite being rated T, Fire Emblem: Path of Radiance almost always uses words like "blast" and "dastard". Ike only says "damn" if he dies (which is also Game Over).
In Gradius V, if you lose your last life after having gone through 6 stages on a single credit, the announcer exclaims, "What the hell?"
In Half-Life 2, Dr. Breen, ever the the classy and intelligent villain, never stating so much as a "darn," let's out a loud and clear "Oh, shit!" when he sees Gordon and Alyx are close behind him during his conversation with an Advisor.
In Team Fortress 2's "Meet the Spy" the BLU spy drops a Yo Momma Joke, quickly followed by a (censored) F Strike. Since the Spy has always been the picture of sophistication, these two combine to be absolutely hilarious.
BLU Scout: What are you, the President of [the RED spy's] fan club?
BLU Spy: ...No. That would be your mother. *produces compromising pictures of the Scout's mother and the RED Spy*
BLU Scout: What the?...
BLU Spy: Indeed. And now he's here to f*ck us! So listen up, boy, or pornography starring your mother will be the second worst thing to happen to you today.
Lost Planet 2 doesn't have any qualms with using foul language when appropriate, but this line from the lead Rounder at the end of Episode 3 takes the cake: as he mans the controls of a railway gun to fight a massive Akrid:
In Castlevania: Order of Ecclesia, the third boss in the game consists of a gigantic crab that the heroine Shanoa must fight all the way up a lighthouse. At the top, Shanoa gets into an elevator, tells the crab to "go to Hell," rides the elevator all the way down, crushing the crab. This is made all the more awesome by the line appearing as a sound bite rather than as a text box.
It bears mention that the original Japanese phrase ("Jigoku ni ochiro.") translates to "Fall into Hell." and, when used in its entirety, is at least somewhat less offensive than its English equivalent.
In the white chamber, though she uses other swear words throughout the game, Sarah uses the F word only once, when she's being shocked in an electric chair and the laser gun beside her doesn't work.
In the final moments of Modern Warfare 2, you, as Soap, get stabbed in the chest by General Shepherd, whom you've been chasing for the majority of the last mission. As you stir, he gives you his Motive Rant, starting:
Shepherd: Five years ago, I lost 30,000 men in the blink of an eye. And the world just fuckin' watched.
In the Japanese audio for Sonic Adventure, Sonic says "shit" once. Translated to something along the lines of "darn" in the American version.
Though it's not as vulgar as the other examples on this page, there IS one moment from the normally G-rated language Final Fantasy VIII that deserves a mention. When one minor character very NEARLY kills another by accident (by hanging him with a fishing line, no less), the almost-victim understandably berates his idiotic pal, finishing up by calling him "DUMBASS!" Complete with red text and a slashing sound as the word as said, to drive home the point that yes, this is as foul as the language is going to get. Maybe they were trying to avoid what happened with Final Fantasy VII.
FFVIII has two other notable instances. One is when Zone, one of Those Two Guys, lays into Squall for letting Rinoa get hurt: "YOU SON OF A BITCH!" the other is when Squall and party overhear fatherly and normally ineffectual Headmaster Cid arguing with Garden Master NORG:
Headmaster Cid: "Greedy son-of-a-bitch! Why did I ever bother talking to you! SeeDs were brought up for the future! And that future is now! Why can't you understand!? Dammit! I should've never trusted you! I wish I could go back ten or so years. To tell myself that you're nothing but a money grubbing son-of-a-bitch!"
And if you've got enough points to make the Renegade speech at Tali's trial:
Shepard: Do whatever you want with your toy ships! But leave my crew out of your political BULLSHIT!
And in the same incident, Kal'Reeger if he's still alive.
Kal'Reeger: Tali's done more for this fleet than you assholes ever will!
And yet another one from Tali's trial, this time if she does get exiled;
Shala'Raan: I don't give a vorcha's ass about the fleet Tali!
Udina's entrance if Anderson was picked to the Council
Udina: — Do the words "political shitstorm" mean anything to you?
In the third game, EDI takes a break from her Spock Speak if you help her romance Joker, saying she called him on his bullshit.
Similarly, in Fallout 3, if you've been playing with positive karma, you get the opportunity to pull one off when you're being captured and interrogated by Col. Autumn, who wants the activation code for the purification device.
Autumn: You tell me that code, and maybe we can work out a deal for you.
The Lone Wanderer: Fuck you. I'm not telling you anything.
Autumn: I'll be honest. I'm running out of patience here, and I'm not looking to play games with you. You tell me that code, or it's going to cost you.
The Lone Wanderer: No, seriously. Fuck you.
You can say this with negative karma, but it doesn't have that same OOMF to it as it does with positive karma.
Burnt Skeleton's placard: We're dying out here, motherfuckers!
Talon Company Merc: "I want this one's head on a fucking plate!"
The biggest one is probably from Madison Li at the end of "The Waters of Life." Normally a cold, but certainly clear-headed woman, she ends up watching the man she harbored unrequited feelings for sacrifice himself, and then had the dream of Project Purity crushed for a second time. After that, her life, and the lives of all her companions are put into the hands of the kid who's a constant reminder to Li of James. Then, finally after narrowly escaping death, she's denied sanctuary at the one place where the group would be guaranteed safety. She sounds like she's on the verge of tears.
Madison: Lyons! I know you're in there, I know you can hear me, you open this goddamn door right now!
In Fallout: New Vegas, a memorable one occurs when after tracking Benny down to the penthouse he's staying in, if allowed to leave he quickly double-crosses the Courier and attempts to murder them (again) by sending up a squad of goons. He then calls over the intercom.
Benny: The cleaners will knock twice. Tell them to be thorough.
Since being a package courier often involves trekking across post-apocalyptic wastelands, often by oneself, it seems no wonder Cass claims that one of the rules of the Caravan Wastes is apparently "Don't fuck with the guy who delivers your mail".
In Dual Destinies, Apollo who hasn't cussed one in the entire series until this point suddenly breaks under the fact that his friend has just been murdered.
Apollo: DAMN IT! IT'S NOT FAIR!!
Then he does it again, twice in the same statement, when he learns that Detective Fulbright was the one who killed his friend.
Apollo: That scumbag killed clay...! Damn it! What the hell was I thinking?!
StarCraft plays both sides of this trope. Units will frequently refer to "chicken-[beep] outfits" and not having time to "f[beep]k around", but in cutscenes "shit" and the like are thrown uncensored whenever it's deemed dramatic enough.
Remember Kerrigan calling herself the queen bitch of the galaxy? The (unofficial) Hungarian version made her the "Fuckin' Queen of the Galaxy".
Bayonetta, surprisingly, as Bayonetta herself actually doesn't swear much in-game.
Some of the characters in Killer7 let these out after hitting a Heaven Smile's weak spot - young punk Con Smith jubilantly shouts "FUCK you!" and shady thief Coyote Smith snarls, "You're fucked." Depending on how good the player is at hitting the Smiles' weak points, this can quickly turn into a Cluster F-Bomb.
Henry Townshend of Silent Hill 4 has a "What the hell?" which is used repeatedly around the first part of the game.
Near the ending of the game after not being able to stop adult!Walter from kidnapping child!Walter Henry says "Damn it!"
Heather from Silent Hill 3, right when Claudia's plan is about to come to fruition: "SHUT YOUR STINKING MOUTH, BITCH!".
Earlier, when the amusement park changes into its nightmare version, "Oh hell!"
In Primal, when Jen encounters her first demon, she slowly looks up his body and to his face and summarizes her emotions with one heartfelt "Ohh... shit!"
Sam Fisher of Splinter Cell hardly ever curses, which is particularly noticeable in Conviction, where he's pitted against Mooks who prefer ClusterFBombs So, throughout the game he has a few that really stand out, particularly when he tells people to go fuck themselves.
In Malta, having no family left, his agency wanting to kill him, trying to find a reason to go on, Sam is pursued by thugs hired by a drug and arms dealer to kill him. After easily (and brutally) taking care of the Mooks, he finds the leader who tried to run away, but ran into a dead end in a bathroom.
Sam: Looking for me, asshole?
In a Flash Back mission during the Gulf War, Sam is captured by (presumably) Ba'athist soldiers and is interrogated by two men, and apparently of the English those two men have learned, half are vulgar terms. When they threaten to Electric Torture Sam, his only response is a quiet, gruff "Go fuck yourselves. I'll be here when you're done." For maximum effect, barge in and rescue Sam right after this point, but right before they start torturing him.
Then there's this exchange. Sam has been shot in the shoulder and had his hands bound by Grim, who for all Sam knew at that point may have still been suffering from Chronic Backstabbing Disorder due to what had been going on throughout the game. He's in front of a similarly captive President, Smug Snake Tom Reed, and about 5 actual highly trained splinter cells, and he still drops one.
Tom Reed: So Sam, how does it feel knowing you're about to go down in history as the man who assassinated President Caldwell?
Persona 4 gives the main character a chance to say "Calm the hell down!" during a particularly... tense... moment after his cousin/surrogate little sister seemingly dies and the main characters contemplate killing the man they think is responsible. The above line is used in order to calm down the protagonist's understandably furious friends and get them to think more rationally. The protagonist can curse several times throughout the game, but the delivery of this is what makes it especially poignant; He YELLS and gets visibly angry for the first, and only, time in the entire game.
The opposite decision's line is just as unexpected, but more chilling: "Throw the bastard in."
In Devil May Cry 4, when fighting Sanctus one of the things Nero will say when using the Devil Bringer is "I'm not interested in your bullshit!", with a punch to the face for effect.
One of the things Nero says when doing a DTd Buster on an Alto Angelo sounds a lot like "fuck you!", but this is somewhat debateable since it's not as easy to make out as the above one.
In Baten Kaitos Origins, Sagi, normally a Nice Guy, will drop these whenever he gets really pissed off.
Go to hell, you son of a bitch! You hurt my mother!
Touhou 8: Imperishable Night, stage 4 with Marisa/Alice. Due to a bad misunderstanding, best friends Reimu and Marisa wind up having an actually for serious fightnote the source material says they play-fight all the time, but this one was actually serious, and we know things got real when Marisa tells Reimu:
Example A: What the eff, guys? Just because Mommy can be a psycho-bitch on occasion doesn't mean you have to cast a sociopath! Example B: Shut the hell up! We were never tools, you stupid asshole! Example C: If Tsubaki were here, she'd give me such shit for sleeping in the middle of an important mission... never mind that I'm on an aircraft and can't do crap, anyway...
Likewise, you know Valkenhayn is angry when his language goes bad (anything regarding Terumi fouls his mood real quick).
"Imbeciles! Don't they realize what that shitty little cur is capable of...?"
The language in The Elder Scrolls V: Skyrim is usually pretty mild, which makes it all the more satisfying when Ulfric Stormcloak calls it like it is in regards to Elenwen (at a peace conference, no less):
Ulfric: To think that we would sit down with that...Thalmor bitch!
Donkey Kong 64 has this line during the DK Rap (to put it in perspective, this occurs in an E-rated game): "He may move slow, he can't jump high, / But this Kong's one hell of a guy!" This gathered huge amounts of complaints from parents, so in the remix in Super Smash Bros. Melee, they changed it to "heck" (despite the fact that Melee is a T-rated game).
Eddie: I told you not to climb on that, you stupid mother—[a notification appears on-screen asking if the player would like to hear the swears, or bleep them]...FUCKING PIECE OF SHIT!
Lars: The time has come for you to SHUT THE HELL UP, Lionwhyte!
Eddie: Dude, how 'bout this? How about you pick up your little baby foo-foo, lay down your diaper, and GO DO YOUR FUCKING JOB RIGHT NOW?!
In Klonoa 2: Lunatea's Veil, after defeating Cursed Leorina, she falls to her knees, crying "Damn it! Damn it all!" In an E-rated game. Also, in the GBA game, Empire of Dreams (also rated E), Klonoa says "Damn it! Not again!" when Jillius' troops spot him in World 5.
Dead Island Riptide does not shy away from the F word at all, for the most part. The exception being Xian, whose reaction to smashing a bulldozer loaded with fuel into the quarantine zone is a small "oh my god." It takes something more than that to set her off, once after the virus causes a massive Berserker Rage, and again at the end where after learning the virus outbreak was deliberate and the victims experimented on and having to stop a crazed, purposely infected Harlow, confronts Serpo who openly admits to causing the disaster to test and later sell the virus.