Pretty much every instance where York smiles, due to the sometimes awkward character facial animations.
Every cutscene including the dramatic ones has the potential to become this if you let York's clothes get dirty long enough to accrue a whole cloud of flies following him.
The beginning cutscene of the game is a great Establishing Character Moment for York, with him fiddling around around on his laptop, while talking on the phone about his theory of Tom and Jerry having a sadomasochistic relationship, while still driving. Even better is only when he puts this stuff away and sees the Raincoat Killer is when he veers off the road. Also while he is veering off the road, a couple of squirrels get startled and make chimp cries.
Every time York escapes from the Raincoat Killer, the killer does a silly Finger Wag and runs off.
If you peep on Thomas in his room at night you can catch him dancing.
Even better, if you talk to Thomas at night while it's raining he'll do the same dance in front of you as he talks.
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.
His dialogue makes it unintentionally hilarious:
Thomas: Die you skanky swine!
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.
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.
In hindsight, a nice bit of foreshadowing, given George's obsession with power.
York retrieving the aforementioned files from the river by literally fishing them out with a pole is one of the most monumentally surreal things in the game.
"For me, he was insane. 100%. Drinking from the skulls, well, that is one thing. But those he had used to relieve himself... He would then just use them to drink from too. That was too much for me. That's just not sanitary."
York getting introduced to the Sinner's Sandwich by Harry and Michael, hilariously awkward rhymes and all.
All the Mood Dissonance whether be it from scene to scene or the happy music being completely incongruous with what's happening on screen.
Forrest Kaysen's first monster form is absolutely ridiculous, especially after he managed to be genuinely intimidating as a human only moments before.
Polly's sidequest has you hunting down a picture from her youth. York will compliment her on how pretty she looked, leading Polly to confess that she came second place in the Miss Greenvale contest. When York asks her who came first, Polly says it was Sigourney. York responds with about as much shock as the audience.
York: Sigourney? The lady with the pot?
At one point after helping Emily with a recipe in her sidequest chain, she happily states that her cooking is getting as good as Thomas's. York politely disagrees by saying you can't compare the two, likening Thomas's cooking to having tea while listening to classical music, taking a very long pause trying to come up with an equivalent simile for Emily's cooking... and then bluntly changing the subject.