Sonny has one about Felicity knifing Veradux in the face. The first time they meet, he almost lines up a shot and she throws a knife at him. The second time they meet, she throws a knife at him as she escapes, prompting a shout of "ow! My face! Again!". When she shows up later and joins your party, Sonny comments "quick, cover your face.". She also has an attack in-game that inflicts a debuff described as the victim having a knife in its face.
Sam And Max: The second ever example of Sam letting Max answer the phone (Look in the Sam and Max entry in Western Animation for the other) occurs in the last episode of Telltale's second episodic season. Hell freezes over, at which point the phone starts ringing and Sam just stands by and lets Max answer the phone. Max also won the Nobel Peace Prize, and Sybil lets him be the official at her wedding.
During the Telltale games episodes, you can ask Bosco for various ridiculous items, which he almost invariably doesn't have, including "hats in the shape of a cow udder", "Self respect" ("Ha, got you!" "No, I understood the question, all too well."), "Vegetables in the shapes of naturalists" (Which is a shoutout to the first game, "Sam and Max hit the road") "Ketchup" (which he does have, but it takes him a second to realize he was asked about an actual thing), and "Weapons of Mass Destruction" (to which his answer was "Who's asking?"). In the last episode of Season 1, Sam asks for items which would have made every previous episode trivial (except the second, where the item either would have been useless or wouldn't have existed yet). He has all of them, and you later find them right behind the lottery tickets.
In season 2, he's not running a store any more, but you can still torment him by asking him, even when he's naked in hell. In the first episode, Sam asks for "passive aggressive payback disguised as innocuous customer inquiry?"
In Tales of the Abyss, every time the party needs to recap anything for an NPC, Jade makes Guy explain. There's no obvious reason why Guy should get stuck with the task. (Mercifully, the actual explanation occurs during a Fade to Black.)
Whenever the party gets involved in something bad in Tales of Vesperia, expect Yuri to remark that he must be cursed.
"The sign of Victory!"
Tales of Symphonia has a few: Raine's cooking being terrible, her fear of water, Colette apologising at every little thing, Lloyd's hatred of Dwarven Vow #7 ("Justice and love will always win!"), Zelos flirting with every girl he meets, Sheena (and Colette's) clumsiness, Raine's love of archaeology, Lloyd's "Give me your name and I'll give you mine" line he uses to anyone who asks him who he is (lampshaded at one point when Genis asks why he didn't say it and Lloyd responds "It's not worth it"), Genis being smart (almost to the point of Insufferable Genius) and Lloyd being dumb, etc.
The bad cooking one turns up in every Tales game, actually. It started with Arche in Tales of Phantasia.
A small gag that occasionally occurs in the Z-button skits involving Zelos and Sheena, after the former says something perverted and/or insulting towards the latter:
Sheena: You better shut up or I'll smack you!
Zelos: Don't say it after you've smacked me!
A recurring joke in Tales of Graces is the messed-up "We are... awesome!" victory skit. Variants include Pascal hogging the screen, Hubert's glasses almost getting stepped on, and even Asbel lamenting that his team is unable to coordinate.
Asbel's desk. It starts off messy and stays that way. Going back to it has him comment how he needs to clean it. Even after 7 years and 6 months... it's still messy.
Asbel: (thinking)"One of these days I'll clean this desk up."
The Tales Series also has some jokes running between games. Observe the following:
Also there's poor Veigue, who, after adding a dash of Ascended Meme and Big Word Shout, can be depended on for a dramatic KUREAAAAAAA in any cameo appearance. Sadly, he doesn't do it in Tales of Graces. For some reason, he's also lurking in the background of every single Tales of Theatre 5-minute short.
There's also a random one poking fun at Perpetual FrownerAsch. In Tales of the Abyss the eternally dependable snark king Jade says "you look like you swallowed a bug...oh wait, you always look like that." And then in Tales of Vesperia, you can find a signboard that details the fighting styles of all the Abyss party members - but all Asch's entry says is "always looks angry."
SimCity also has a strange fascination with llamas, starting from the medium simulation speed setting in 2000 ("Llama"). 3000 had a llama giving you the Tip of the Day, in The Sims the minor-league team where you could play in the sports career is The Llamas, and the llama love is brought back in Sims 2: University (the llama is Sim State University's mascot). SimCity 4 kicks this up a notch with a cheat code which turns your advisers into llamas.
SimCity 3000 also has running gags with kitty kibble shortage, broccoli (carried over to SimCity 4), and Fourth Wall breakage.
SimCity 4, meanwhile, has running gags about you living a life full of luxuries.
Spore has an homage to this line — if you're loading a game in the Creature Phase, one of the phrases is "Reticulating spines".
The Sims 3 continues with this running gag, as well as the one with Llamas.
The reviewer The Spoony One was pissed that The Thing PC Game had so many fuseboxes you had to waste time on to open doors, and had a "Fuse Box Count" that popped up whenever you saw one. Since then, it pops up whenever you see a fuse box in any other game.
He also reused the Hollywood Squares gag in his Let's Play of SWAT 4, shouting "You FOOL!" whenever the AI partners dropped a flashbang in his face.
Throughout the series, the characters debate on the correct denomination of a ladder (ladder or stepladder?) whenever you examine such a object. The ladders first appeared for flavour, then just for the sake of the Running Gag, and never had any relevance to the cases, except in the third case of Apollo Justice, where examining a (step)ladder clues you into a possible escape route for the murderer.
There's also a running joke in the first game about how difficult Edgeworth seems to find getting witnesses to state their names and professions.
There is also Wright presenting the Attorney's badge, something that nearly every NPC in the first game reacts to (future games restrict this to giving reactions to only recurring characters), often questioning why he is doing so (possible joke at the process of Try Everything). Lampshaded in Apollo Justice.
And then there's Gumshoe telling him that real men wear a police badge.
Detective Gumshoe and his constantly falling salary, pal!
In AAI, we have Edgeworth always yelling "Nnnghoooh" during moments of distress. And Edgeworth will cringe at it every time Kay Faraday brings it up to make fun of him.
In Mario & Luigi: Superstar Saga, no one knows who Luigi is, even Bowser, who calls him "Mr. Green Mario Brother Guy". Likewise, in Paper Mario 2, where Mario was repeatedly mistaken for Luigi in one side quest even Luigi's biggest fan thinks Mario (dressed in green at the time) is Luigi, which in a moment of hilarity the real Luigi shows up which the fan accuses Luigi of being the impostor and calls the police.
In every game in the Paper Mario series except Paper Mario: Sticker Star, there is some variation of a group of wizards whose names all start with Merlon who always tell some sort of long, boring story, during which Mario falls asleep. When he wakes up, they ask "Are you even listening?" to which Mario replies with a nod.
And there's also the tendency for important elderly characters to not say Mario's name right.
Paper Mario: The Thousand-Year Door had at least one NPC say Mario's name wrong, mistake him for someone else or have him go by an alias in each chapter, up until Chapter 7. Examples include the "Luigi" example mentioned above from Chapter 6, an elderly koopa mispronouncing his name as "Murphy" in Chapter 1, and Mario going by the alias "The Great Gonzales" in Chapter 3.
The characters from the Atelier series (and its spinoff, Mana Khemia) seem to have an unhealthy fascination with barrels, and will shout "Barrel!" every time the player examines one.
Lampshaded in Mana-Khemia 2: Fall of Alchemy and Atelier Annie. In the former, Pepperoni and Goto (later replaced by Lily and Whim) surround a barrel in the Campus Grounds and notes "it's a barrel", while in the latter, a customer will lament the lack of barrel once your shop level is high enough.
In Super Robot Wars, the tendency of Elzam's Leitmotif '"Trombe!" to override all other songs is taken as a Running Gag by the producers. But then Flanderization took over, and due to the awesomeness of the song, and it's no longer viewed as a Running Gag, but justified by the Rule of Cool. In the RPG spinoff Endless Frontier, there's a running gag involving Kaguya Nanbu being mistaken for or compared to a cow, due to her... huge tracts of land, and possibly her white-and-black outfit, including by what's essentially a minotaur. Who asks to marry her.
Half-Life 2 also has a run-on joke from Half-Life, where guards would sometimes reply to "use" with "Catch me later, I'll buy ya a beer", and having Barney (the one personification of all the 'Barney' NPC guards throughout Half-Life) tell the player "Now... about that beer I owe ya!" as his first line to the player after revealing himself.
Mentions of Wirt's wooden leg in the Blizzard game Diablo have spread to the other Blizzard game Warcraft (and all sequels/spinoffs that follow).
The Overlord series and pumpkins. In the original game, it was restricted to your minions being able to wear them as makeshift helmets and a farmer who treated them as sinister Companion Cubes. Raising Hell upped the ante by adding Killer Pumpkins and the Mama Pumpkins that create them. From then on, pumpkins and characters bizarrely preoccupied with them have been a comedic fixture of the series. Gnarl put it best in Overlord: Dark Legend when he said "Damn pumpkins! Laying around all day... being orange."
In the Sonic the Hedgehog series, starting with Sonic Adventure 2, Amy thinks someone else is Sonic, runs up behind them out of nowhere, and hugs them, and seconds later Amy sees she was mistaken.
Ever since Sonic 3 And Knuckles, Knuckles has the tendency to believe in Eggman's lies that Sonic is the bad guy, leading him to fight against Sonic until he realizes that he's been duped by the evil scientist.
Apparently, Nasu took a great deal of interest in the character popularity polls of Tsukihime and the fandom's reaction to certain characters who have been Demoted to Extra, becoming the source jokes in the fandom and ran with it in Kagetsu Tohya. The result? Ciel constantly paints or outright breaks the fourth wall out of depression for her low popularity. In the side story Ciel Sensei, she eventually teams up with Kohaku (whose Batman Gambit nature was also downplayed and turned into a joke) against Arcueid because she's the only heroine to score lower in popularity. Satsuki is eventually kicked out because she never actually got heroine status and can't answer questions about her route.
On the comp.sys.sinclair newsgroup, every "what is this game?" request will get at least one reply to the effect that "it's definitely not Stonkers". This is sometimes subverted, e.g. if the game described is a Platform Game, someone might reply "it's definitely not Jet Set Willy".
Given your party's status as a walking band of racial stereotypes in Neverwinter Nights 2, some running gags are unavoidable: Khelgar's constant belligerent drunkenness, his constant insistence that Elanee is underfed, Shandra's constant complaints about being a farmer stuck on an adventure, and Grobnar. No more need be said about that last one.
Most of the 3D Zelda games have a running gag in which Ganondorf can be defeated with normal household items:
In most games, attacking the cuccos will result in Link being mauled by an invincible army of them until he leaves the area. However, in Twilight Princess, attacking them will allow you to swap bodies for ten seconds.
Most Zelda games since A Link to the Past begin with Link being asleep and someone/something waking him up.
In Skyward Sword, Fi always makes reference to the Bokoblins' obsession with "fashionable undergarments" when analyzing them.
Tingle and his obsession with fairies and driving you bankrupt.
Final Fantasy VIII has a subtle one: no one ever shakes Zell's hand. He'll offer and be ignored. Everyone else will get the offer to shake hands (Squall usually won't do it) except Zell. He's eventually put out by this, but, being Zell, shakes it off. He can't get any hot dogs either (flavored bread in the original).
Barrett's train metaphor comes up a few times, though it's only a memetic occurrence.
For Final Fantasy in general, we have Gilgamesh, a recurring Plucky Comic Relief boss character that is technically the same guy from Final Fantasy V (Not a rehash, the same exact person), just caught in the endless void of dimension hopping who shows up in other games in the franchise. Even those that were made before Final Fantasy V.
The Grand Theft Auto games have several running gags within their in-game radio stations and commercials. These include:
A war between the United States and Australia.
"Freddy needs a nanny, because he's been a very naughty boy!"
DJ/Talk show host, Lazlow (who's actually a real life talk show host who wrote some of the dialogue for the game), getting fired from one radio station and hired by another by the next game.
Black Isle / Troika has regular instances of Squick / Black Humor bestiality. Fallout 2 has an omnisexual farmer's son. Arcanum has a sheep as a worker in a brothel (that the player can purchase the services of) and Temple Of Elemental Evil has a cut content brothel that also included an option with a rooster.
Linear RPG has Kliche waking up wet every single time.
Bayonetta features Enzo's car getting smashed up as one of these.
It is guaranteed that any more games in the Dragon Age franchise are going to include Sandal standing in a room full of dead Darkspawn/demons including multiple Ogres and Pride Demons, and responding to any questions about what happened with "Enchantment!"
Shale's hatred of birds, to the point of a shopkeeper in the second game telling Hawke a story about a massive decline in the Ferelden pigeon population.
All the suggested/past offscreen references to Oghren taking his pants off, always reacted to with either shock or horror.
Alistair's catchphrase "Swooping is bad" from the first game became this in the second. Whenever someone as much as used the word "swoop", somebody is bound to bounce it back (e.g. by Alistair's himself in his cameo and by Varric during his random banter with Merrill in the Legacy DLC).
Mass Effect 2 has a turian outside the Wards that repeatedly tries to get through the security checkpoint. Every one of his exchanges with the security officer ends with him saying "You humans are all racist!"
Similarly, the first game has the human trying to return a product at a shop in the wards.
He's still there in the second game. Two years later.
In Mass Effect 3, you can help him get his refund for his 15-credit toaster.
Reporter Al-Jilani getting punched due to Shepard having had enough of her adjective nouns. In a bonus video from the Lair Of The Shadow Broker DLC, she gets punched out by a krogan. And, if you got back later, by a volus! BioWare must really hate reporters like her... In Mass Effect 3, she also tries to punch Shepard back. Shepard can respond by headbutting her.
Any time you happen upon dead bodies with Grunt, there's a good chance Grunt will ask if anyone else is feeling hungry. Given a Call Back in the third game if Grunt survives holding off the Ravagers.
Commander Shepard's dancing being hilariously atrocious.
The automated announcer's comments about various "apocalyptic scenarios" during the first test chambers.
GLaDOS taunting Chell about her adoption and Parental Abandonment. This is also a Call Back to an offhand claim GLaDOS made in the first game. Similarly, GLaDOS taunting Chell about her supposed weight issues. Wheatley tries to get in on these gags later, only for GLaDOS to hilariously shoot him down.
Chell being a Heroic Mime and the other characters commenting on it. Similarly, Chell supposedly having brain damage from extended hibernation.
Wheatley is a living fountain of running gags: catching him when he falls, his ineptitude at hacking, his inability to accomplish things without Chell's help, GLaDOS' insistence on calling him a moron/idiot, his ineptitude at designing test chambers, his ineptitude with Death Traps, and more. Let's just say that his ineptitude in general is the biggest running gag of the entire game.
Suikoden series has a few, most notably the "Schtoltenheim Reinbach III" pseudonym and Viki sneezing and teleporting herself to another game events during the victory feasts at the end of the games.
One of the missions in City of Heroes sends the player character(s) to rescue a Dr. Stephen Fayte, who is constantly being mistaken for a powerful sorcerer even though he is "merely a gifted surgeon, and nothing more." His captors repeat this phrase verbatim several times when he's found, as if they're under the influence of a Jedi Mind Trick ... but that's impossible, for Fayte is merely a gifted surgeon, and nothing more.
Tidus waking up on a new shore after Sin attacked; it happens like 7 times over the course of the game. It's also the manner in which he is revived in Final Fantasy X-2.
Pokémon Ranger: Shadows of Almia and Guardian Signs both repeatedly mention people being "bound up with rope tied a smidgeon on the tight side."
Halo: Reach probably qualifies, given the number of times after a cutscene Noble Six is getting up off the ground and picking up a gun.
The Elder Scrolls games begin with the main character locked in prison for some reason or another with alarming frequency. Usually you're freed by the Emperor to aid him in some manner. Subverted for once in Skyrim, where instead of being locked up in prison, you're on your way to be executed.
In Morrowind, there were three separate instances of nude Nord barbarians, as a result of them offending the witch they were escorting. Later spoofed in Tribunal when you found another nude Nord who was quite vocal about having never escorted a witch; he's nude because Mournhold is hot.
M'aiq the liar who shows up in every game from Morrowind onwards (either the original or his great great grandson) to make Fandom Nods and Take That comments about the fans and devs alike.
Fallout features a running joke and Mythology Gag in the form of Harold, a FEV mutant with a tree called Bob (or is it Herbert?) growing out of his head. He shows up again in Fallout 2 and makes jokes and references to the first game. Finally in Fallout 3 He shows up again, completely mad from his 200 years of life and still very friendly.
Fallout: New Vegas also has Cass and a few other NPC's who will make jokes and snide remarks about events from the second game.
News tickers during pre-mission cutscenes in the first two Splinter Cell games make mention of a US Army general named Fisk, who suffers his third heart attack in the first game, and then his fourth and final one in Pandora Tomorrow.
Every single Dragon Quest game has a reference to "Puff Puff", at least in the Japanese version. It's seldom spelled out directly, but in most cases implied to be Marshmallow Heaven.
Additionally, every game that includes a Dharma Temple/Alltrades Abbey will have, somewhere in said Temple/Abbey, and old man who wants to be a young girl. It varies from game to game and translation to translation whether he simply wants to be a little girl or a Bunny Girl, though.
Pokémon main series games and their ever-present Fisherman with his team full of Magikarp.'
"Shorts Kid", a variant of whom has showed up in every generation.
Every game features a Hiker who starts each battle by laughing and ends it by telling you he has Hay fever
One such example would be the dog whistles that each member of the family carries which, when blown, will have Wanko come running if she is within earshot. Unfortunately, this response is so deeply ingrained that her feet respond automatically, causing it to often be used against her, particularly when exam time comes around and there's studying to be done. Exploited for Mood Dissonance during her route, when Yamato uses it to locate her after she's run away from home.
The anime has one for Miyako starting episode 2 - each episode begins with an attempt by her to win Yamato's heart through increasingly ridiculous means, all of which fail.
Live A Live includes a pair of son-father (son will always be called Watanabe or variations of thereof). In various timelines, the father will always have the worst of luck of being killed randomly and then his son would hilariously cry over his death and drag him away. They could be encountered naturally, or require some tinkering in how you play.
From Up Your Arsenal onwards, the series has a running gag in the form of Dr. Nefarious's unfortunate tendency to seize up and broadcast Lance and Janice, the plot of which becomes increasingly ridiculous with each new episode.
In the Nancy Drew game series from Her Interactive, you seem to be following a still-unseen weirdo named Sonny Joon from one game to the next. Wherever an investigation takes you, doodling, UFO-obsessed Sonny is likely to have worked there, vacationed there, or corresponded with someone there, only to leave some time before your arrival. Also, references to Koko Kringles and Krolmeister show up at least once in each game
Pikmin 2: Louie is obsessed with food, to the extent that he is far more concerned with documenting the culinary uses of the various predators he encounters than working out how to survive when faced with them.
Robopon has destroying Dr. Don's time machines every time you return from the past in the second game.
Getting a Snorkel to breathe underwater. This happened in both games.
The Kid's typical entrance into an area in Bastion is to just come flying in and land right on his face. It eventually stops being funny by the end of the game when, after a vicious beating by the Ura, the Kid returns to the Bastion in his usual manner...and then doesn't get back up.