Otacon: "That blade in his hand is called the Master Sword, also known as the "Blade of Evil's Bane". He also has a whole arsenal of items at his disposal— bombs and arrows, a shield, a boomerang and a Clawshot. He's a force to be reckoned with."
Snake: "Gear is only useful when it is used at the right time and place. Just lugging a ton of it around doesn't do you any good."
O: ".... I... uh... I wouldn't be talking if I were you, Snake."
While most likely a developer oversight, when you are captured in Knights of the Old Republic, you can lie and say you don't care about Carth/Bastila during a torture session but the torturer will claim it is an obvious farce because you traveled half way across the galaxy with them. Considering he was the mentor of one of the people he is torturing...
KOTOR II has this meta-example from its own endgame:
Sion: You... seek to erode my will. You will not succeed. [You have eroded Sion's will, reducing his Will saves, Constitution, and Wisdom.]
OWI said in the manual that they did a thorough investigation of Sobe's history of human rights and such before "proudly" advertising for them in-game.
Kingdom of Loathing example: In the "South of the Border" zone, one of the encounters is a cock-fight. You can bet on the favorite, bet on the other one, or walk away. If you choose to walk away, you get this text:
This flagrant display of cruelty to living creatures disgusts you. You decide to head back to the Icy Peak and eviscerate some more Yetis.
In Dissidia: Final Fantasy, Kefka dismisses Sephiroth as "just another sadist with a god complex. Like THAT's anything special!" Being the story's Meta Guy as well as an honorary "sadist with god complex" himself, Kefka seems fully aware of (and amused by) this hypocrisy.
Also in Dissidia, Quistis is the ingame tutor for equippable items, and stresses its importance. When you realise that her origin game doesn't make use of equipment outside of weapon upgrades...
In BioShock 2's Multiplayer mode, noticeably overweight bourbon magnate Buck Raleigh sometimes has this to say while researching a fallen enemy: "Gotta be fit to survive down here, friend!"
A cute example of this trope can be found in Professor Layton and the Unwound Future. Both Layton's apprentice Luke and his adopted daughter Flora strongly dislike being away from him; Luke feels it's his duty to always watch Layton's back, while Flora has separation anxiety. At one point in the game, Layton disappears for a brief period.
Luke: I hope we find the Professor soon...
Flora: Poor thing! You're just lost without him, aren't you, Luke?
Tali: 67: holmium. Very reactive, very magnetic! Garrus: You know, turian parties don't usually end with someone reciting the elements. Traynor: 68: erbium. Atomic weight: 167 and change! Tali: Right, my turn. 69.... Jack:In your dreams! Tali: What? I don't get it. Traynor: I'll explain later. Garrus: It's thulium in case anyone's still interested. Turians have trace amounts of it in our skin. Helps protect from solar radiation. Tali:Neeeeeeeeerrrrrrrrrd!
There's an instance of this that's fairly easy to miss, early on in Apollo Justice. The defendant in the first trial remarks " As I expected. Your eyes and ears are as sharp as your hair." to Apollo... but, if you recall, the defendant is Phoenix, who's rather legendary in the court for having spiky hair.
He probably meant it as a compliment, given how proud he was of his own hair.
Tatsunoko vs. Capcom: "I guess even kids can become heroes in Japan. That must be one crazy country." Well, then, Frank, how about your own country?
In Ultima VI, you have to determine who is the most humble person in New Magincia (which has humility as its Hat) in order to receive the Rune of Humility. Practically everyone will boast about their humility and list the luxuries they've given up and the lowly and humble tasks they've taken up, to prove how exceptionally humble they are. The one exception is the fisherman, who doesn't care about it but is fairly sure he's not particularly humble. You can probably work out the rest.
Comic Book Guy: Videogames, what a waste of money. Now to go online and bid $1,000 on Itchy & Scratchy corn-cob holders! A terrific, terrific expense.
Quite common in the Postal series. For instance, in Postal 2, the first hate group you come across is "Parents for Decency", a group of parents who are opposed to violent video games. They attempt to stop the creation of such games by storming the Running With Scissors offices with guns, after that point they will open fire on the player without provocation, and much later in the game you can find a group of them playing arcade games in the mall.
In the Pokémon RPGs, Red, Blue, Yellow, Leaf Green and Fire Red, there are SNESs situated beside TVs in the Celadon Department Store. When you examine one of them the text reads "An RPG! There's no time for that!"
Glottis: It's not just a job, it's what I was created to do! If I get any farther away from a car than this, I'll get sick and die! It's like I'm not happy unless I'm breathing in the thick, black, nauseating fumes!
Manny: *takes a very long drag of his cigarette* I can't imagine...
She sometimes comments negatively on other female characters' choice of revealing outfits, as well on Joe (and Hwa Jai) for wearing only boxers. When she is criticized for (or reminded of) her extremely Stripperiffic outfit, she says that her case is different as hers is "traditional garb passed down from [her] ancestors!"; however, the fact that she is ocassionally seen wearing something very revealing outside of the ring doesn't help her case.
In Transformers: Fall of Cybertron, Megatron demolishes one of Starscream's monuments to himself, citing it as an example of fruitlessly wasting Energon. All the while other Decepticons tear down more of Starscream's statues. Not mere seconds later, an even bigger statue of Megatron is flown in and set down smack dab in the middle of the courtyard where the scene takes place. Given the game's rather G1-esque spirit, this is almost certainly deliberate.
Batman: Arkham City has a bit of Enemy Chatter where a crook says the first thing he's going to do when he escapes Blackgate Prison is get a beer, explaining that he's in for DUI. Another prisoner admonishes him not to go driving while drunk or he could kill somebody; when asked why hes in Blackgate, the second prisoner says, matter-of-factly, "Manslaughter".
In Dynasty Warriors 7: Empires, if you manage to continually defeat Dong Zhuo without capturing or killing him, he will eventually say this line if you encounter him one more time:
Dong Zhuo: You are a villain that must be eliminated! I will be the person to do it!
Comically ironic, given that he is a major villain himself.