Per wiki policy, Spoilers Off applies here and all spoilers are unmarked. You Have Been Warned.

Dante's reaction to Trish breaking into his office on bike. And then the first thing he assumes is that she's just looking for a toilet.
Dante's cocky attitude in general. A giant lava spider-scorpion thing? He just knocks on its shell saying how he hopes there's "something inside that big body" of his.
The scene where the bridge breaks while Dante is crossing it so Wile E Coyote-esque it's hilarious. The only thing missing is the 'yikes' sign.
"Flock off, featherface!"
- And after the fight against Griffon, the scene leading up to his death. The way his body starts to magically ascend to the heavens before being crushed by a pillar is absolutely hilarious.
After Dante returns to the castle, he often notes that doors that were there before vanished "due to evil powers". In some cases, you almost can feel the snark.
Dante: (after inspecting where door should be) "The door's been vanished due to evil powers. Scary..."
- In fact, when you first enter the castle at the beginning of the game, Dante will often express his absolute disinterest in everything of note he sees.
  Dante: (Inspecting a statue) "This must be a statue of a deity the islanders worshipped. Yeah, whatever."
- Said statue is actually Mundus. Dante just insulted the Big Bad Satanic Archetype without even realizing it.
- Examining the various books scattered around the castle will prompt Dante to briefly describe their contents...only to question why he's reading them in the first place.
According to Hideki Kamiya, the dragon that Dante summons against Mundus is named Puff. Yes, this is a real thing. The hilarious thing about this is that Dante is definitely immature enough to name an eldritch monster tamed by Sparda something like Puff.