The scene early in the game where York has breakfast with Polly nearly had me in tears. There are no words...
Thomas in the Clock Tower after he's completely lost his mind. He swings across the clock tower in his sister's dress and make-up shouting about how Emily stole George from him. The whole thing is just so ridiculous and bizarre that it becomes hilarious, but at the same time you can't help but feel sorry for the poor guy.
Keith is a jovial rock 'n' roll fan who likes to tell ghost stories and play air guitar. He falls victim to the effects of the purple fog with the rest of the townsfolk near the end of the game— and he has a chainsaw at the ready. Having such a happy character wield such a psycho weapon out of nowhere is jarring— and really funny. Where did you get that, Keith?
It's even funnier if you stole his Grecotch guitar, because it seems like he's figured out you stole it.
Zach stepping on Kaysen's doll as he leaves the final fight area with Emily's dead body.
George agreeing to go with York's hunch about going to Velvet Falls to find lost files, under the logic that waterfalls give power, so even if they don't get anything there, they'll be stronger. Emily's reactions sell the scene as well.
York retrieving the aforementioned files from the river by literally fishing them out pole is one of the most monumentally surreal things in the game.
