The episode, "Incident at Chlorine Lake", where Bill the Lab Guy is in an observation cage, watching the Trophy Bass. Then it starts ramming the cage, super dramatic music plays, and Bill yells, "Oh no! I was afraid of this!" The combination of absurd imagery, the music, and Bill's tone of voice makes it a really funny scene.
"Yay! The mayor's toast! Boooo! So are we!"
From "Big Baby":
After the Mayor unveils the big baby at a circus sideshow:
Thunder Girl: Awww, it's a witsy-bitsy baby! Stinky Diver: Blimey! It's a grotesque parody of human life!
Stinky: Smash it, crush it, destroy it! Bill: No, Big Baby's a rare creature, to be studied, not destroyed. Let us use reason, not violence. Chief: Say, um, Bill, there's something we've been meaning to tell you. Thundergirl: Uh, yeah. Big Baby sort of grabbed your daughter, Quarky, and ran off with her. Bill:That thing has my daughter? Aaah! Smash it, crush it, destroy it!
Any time the Chief says "BLAST IT!"
The Body-Eating Virus episode has the Flesh infected with the dread disease. Bill shows the heroes video feed of what's happening to him... and we see a game of Pac-Man.
From the same episode, the League have been infected, and are all reduced to just heads.
Announcer: Meanwhile, the League has gathered together for a touching, final farewell...
Chief: Blast it! If I had any legs left, I'd stomp all you fool-heads into the ground!
When the League is on trial for their incompetence, and the Flesh is the only one who has yet to make a defense statement.
Chief: (Looks to the camera) Well, we'll see you at the reunion show!
The Chief's reaction to the League being cloned in 'Tears of a Clone''
Chief: AAAHHHH!!! HOLY MOTHER OF MOTHERS!!
Leagues: Hi, Chief!
Bill the Lab Guy: Oh no, I was afraid of this.
Chief: No, you weren't, you pointy-headed geek! I WAS!!
Stinky: Blimey! Is the League about to become a buffet for a B-movie behemoth? Narrator: Errr... that's what I was gonna say.
This exchange at the end:
Admiral: Commence bombing! Bill: Wait, you can't! Not just for me, but for the love of science, the love of knowledge, the love of... sequels! Admiral: Sequels? Cancel that order, gunner! We've got a franchise to protect! League: Yay! Narrator: Not nearly the end... (During this time, the covers of Yurplastic Park's sequels are shown: "Yurplastic Park II: The Lost World", "Yurplastic Park III: It's Still Lost", and "Yurplastic Park IV: Now Where Did That World Go?")