As Drake is jumping out of a plane that is going down, he recounts how to parachute out of a plane (jump, count to 5, pull the rip cord), and when he does, he goes into full on Motor Mouth and Oh Crap mode, counting to five in less then a second, and screaming, especially when he finds out that the parachute has a hole in it.
A very funny conversation between Drake and one of the guards in the intercom - Drake tries to con them in Bahasa Indonesia.
Guard:Halo?
Drake:Buka pintu! (Open the door!)
Guard:Siapa ini? Bicara Sekarang! (Who is this? Speak now!)
Drake: Ah, crap...Sialan lo! Cepatan, buka pintu! (Damn it! Hurry up, open the door!)
Guard:Ah, tai! (Ah, shit!)
And the door opens! Drake laughs, convinced of his own genius...and is then greeted by unhappy men with guns pouring from the entrance.
Elena's response to Nate asking if she can use a gun.
Elena: Sure. It's...like a camera, right? You just point it and shoot.
Nate: Good girl!
As Drake is about to go into a dangerous-looking cave, Sully warns him to be careful. His response is "Aren't I always?", which is when he bashes his head against the top of the entrance.
Nate: Ow! I did not see that!
Among Thieves:
Many times in Among Thieves, but the shining star is when Elena asks Nate how scared he was that she was going to die on a scale of one to ten. (She got a four.) And Nate's denial that he cried.
Nate: It was raining and you were unconscious.
Elena: It was sunny and you were bawling. Whatever, I kept your tears in a jar. I have proof.
"How the hell am I supposed to take out a - hell-o?"
"I'm sorry, do you have a plan to go with that grenade?"
Nate's hand puppet show after getting put in jail in the second game, re-enacting the final conversation he had with Harry Flynn when Flynn was betraying him, ending the show with puppet!Drake apparently shooting puppet!Flynn in the face.
"Hey, jackass, you're ruining the show here."
Chloe, Flynn and Nate, after discovering their employer has sent them after something vastly more valuable than they had assumed:
Chloe: So. We're dicking this guy over, right?
Nate and Flynn: (in unison) Yes.
"There's a guy above you, there's a guy above you!" (Drake tosses guard off roof.) "There's a guy below you, there's a guy below you!"
Nate and Chloe climb to the top of a ruined hotel to discover a rooftop pool. If the player has Nate jump in and swims around, it triggers a conversation:
Nate: Hey, check it out: Marco! Chloe: Really? Nate: C'mon! Chloe: No. Nate:(still swimming) Marco! Chloe: ... (sighs) Polo. Nate:(gets out of pool) FISH OUT OF WATER! Chloe: You are so unprofessional.
Ironicus had a long giggle about that one when he discovered it.
Nate griping about anything and everything while climbing up the train in Chapter 15.
In the same vein, Nate heroically leaving everyone else behind so that he'll fight Lazarevic alone, and then bitching about what a stupid move it is the moment they're out of earshot.
A lot of Nate's comments while fighting his way through the train. Highlights include trying to warn enemies of the warning lights along the railway, to yelling at enemies for shooting at him while he is chased by a gunship.
As an addendum to the first bit, Drake reveals in said scene what he uses as a "ten" baseline on the Fright Scale:
Sully returns with a pair of sawed-off shotguns and hands one to Elena, leaving Drake weaponless.
Sully: (off Nate's look) What? He only had two.
In the flashback with kid!Nate, blink and you'll miss it, but when Sully sets down a beer and a fizzy fruit drink with lunch, the kid reaches for the beer first.
Most things that come out of Cutter's mouth are hilarious, especially when interacting with Nate.
His almost girlish reactions to enclosed spaces are also a sight to behold.
Towards the end of the final chapter, when Nateinadvertently causes the entire city of Ubar to collapse.
Sully: Three Goddamned bullets. How the Hell did you do this with three Goddamned bullets?!
"So then the guy says: 'Well, you better tickle mine too, 'cause now I gotta catch the Goddamned thing.'" Oh, Sully.
Similar moment:
Nate: You do realize you make everything sound dirty.
Sully: I do?
And the payoff:
Sully: Well, at my age, a bird in the hand, you know?
Chloe: Ew.
Nate: You see?
Sully: Alright, alright!
Nate and Sully's reunion after Sully supposed "death". Nate points a gun at him and questions how he's supposed to know whether Sully's real or not. Sully just walks up to him, takes the gun, flicks Nate on the nose and then tells him never to point a gun at him again.
Made even funnier when you consider that the nose flicking is likely how he may have disciplined Nate when Nate was a kid.
Nate commenting that a clapped out old rustbucket is Sully's first car. Made even funnier because Sully seems genuinely interested about it.
Nate's notebook has a sketch of a couple of objects he and Sully passed by (including what looks like an old popcorn machine) with WTF ARE THESE?! written underneath.
A quick gag in the Yemen level. Nate is Parkour-chasing Talbot through the backstreets and ultimately into a hotel. Talbot runs through an open door, and when Nate follows, Talbot slams the door in his face and locks it. Nate, knocked off balance, staggers around and crashes through a different door - which opens into the same room.
The part where you got a convoy of trucks with machine gun firing at you. Marisa Chase tells Drake that she saw explosives with the convoy. Drake replied with something along the lines of "No no no, that's not a good plan." Then the canvas covering the backmost-truck flips open, revealing a truckload of guess what.
Nolan: I think what attracts Nate to Elena the most is the fact she's compassionate -
Emily: (nods)
Nolan: She's intelligent.
Emily: (nods)
Nolan: And she's - we're talking about Elena.
Emily: Yeah! I get it.
Nolan: So just... relax. Just cool the jets.
During the production of Drake's Deception Nolan North put together a book to showcase the sheer amount of skill and effort that goes into a game series like Uncharted. It's full of insights into the industry... and it's really freakin' hilarious. From the notes on the motion capture for the horseback scenes:
During one of the mocap sessions we had to capture me riding the horse as if in a full gallop. This required me to bounce up and down in the saddle like an idiot for a full minute. It was one of the most ridiculous things anyone had ever seen. A grown man in a skin tight suit bopping along on an imaginary horse. Just when I thought it couldn't get any worse, the stage was suddenly filled with the "My Little Pony" theme song blaring from the speakers.