Doing It for the Art: The team at Naughty Dog could be called insane for the amount of work they put into these games. From doing motion capture and dialogue recording at the same time to squeezing every last bit of power out of the PS3's Cell Processor, the effort they go through to produce this amazing experience goes far, far beyond what is required to make these games a success. They don't just go the extra mile, they pave the road for everybody else.
Dyeing for Your Art: Nolan North mentioned in an interview that during parts of the motion capture for Drake's Deception, he was suffering from broken ribs. While clearly not done intentionally, it meant the pain and anguish on Nate's face is actually real.
Claudia Black: I saw the casting call and it said "character speaks with an undefined accent, maybe British, maybe Australian, maybe European", and I thought, "Well, I can't not get this part, I can do all three!"
In another universe, Eddy Raja was an unlucky Cabbage Merchant among other voices.
Jossed: This seems to have happened to David O. Russell's concept for the film (before he quit), in which Drake's family apparently played a large part. As of Drake's Deception, we now know that Nate was raised in an orphanage, and Sully's effectively been Nate's substitute father since he was a teenager.
Throw It In: Many of Drake's one-liners were improvised, including the classic "I will kick you to sleep!"
The line "Aw, kitty got wet!" was thought of by Nolan North (Nathan's voice actor)'s son while playing Wii tennis, which leads to it being one-upped with this random line during multiplayer. Referenced in Uncharted 3. "Aw, what's the matter? Kitty don't like getting wet?"
During a recording session for Uncharted 3, Nolan North watched a scene of Sully crossing a beam very wobbly, and immediately shouted "What are you, drunk?!" To which Sully replied, "Maybe..."