Elena salvaging Drake's ring after Nate leaves it with sir Francis.
The final scene where we discover that Elena's all right and she and Nate finally share that kiss. Final line in that scene doubles as a Crowning Moment of Funny as well.
In Nate's diary, amongst the mementos, goofy doodles and notes about treasure is an unexpected fuzzy moment - a detailed sketch of Tenzin's tiny daughter, Pema, wearing a sweet little smile. Awww.
The flashback to Nate's childhood and Sully turning on Marlowe's men to save a kid's life.
Chloe's reaction when Charlie's hallucinating due to being drugged, and trying to kill Nate. A far cry from how selfish she was in the second game, she constantly tries to help him snap out of it. It's likely that if she wasn't there, Sully would have shot Charlie point blank.
The fact Sully was willing to shoot Cutter in the head just to save Nate. He even distrusts him for a while afterwards, until he helps him after Cutter breaks his leg.
At the closing of the second act, Nate staggers back to Elena, utterly exhausted from being held hostage and trying to find Sully. Nate's about to turn around and head back out, but Elena makes him lie down and rest, with his head in her lap, and even strokes his hair. Made even more adorable when Nate takes her hand, and apologises to her.
Also doubles as a Crowning Moment of Awesome for Nate. Sure, he's been beaten within an inch of his life, he's tired, he's hurt, he damn near drowned, and he clearly can barely even stand up. But Sully is in trouble. That's the only thing that matters to him.
The fact that losing Sully is clearly what Nate fears the most during Drake's Deception.
The end of Drake's Deception with Sully's fatherly speech to Nate, and Nate finally wearing his wedding ring again. Made all the cuter when Elena mentions she's sorry that Nate lost Drake's ring, he just responds that he replaced it with something better, and shows her his wedding band. Aww...