In the first cutscene, right before Lawrence re-animates the Light-Eating Z'Grute, Nefarious screams in his ear like normal...only with a megaphone.
After Nefarious repairs Commander Spog Qwark insists that Nefarious did the right thing. Nefarious's response?
Qwark: You did the right thing, Doctor!
Nefarious: Get bent!
The repair itself is also pretty darn hilarious. Nefarious winds himself up as if he's preparing for a delicate, artistic procedure, and then just performs an off-screen Percussive Maintenance, finishing with kicking Spog in the head. The scene receives a cherry on top when Spog's start-up is accompanied by a musical riff suspiciously similar to the Windows start-up jingle.
This exchange in 'The Presidential Retreat;'
Qwark: You know I'm actually starting to like it here? Sure, it's a dangerous planet riddled with murderous robots and exotic predators. But take away all that and what do you have? A presidential retreat-slash-water park!
There's also the Octonok Cay Tharpod, who tempted fate by saying that he was going to live the rest of his life free of tragic irony. There's a surprisingly long delay between this line and any further action, and you almost think that he's going to get away with it. Then the King Sepiad eats him. After scaling the lighthouse and beating the King Sepiad, the player(s) have probably written him off for dead, but as soon as the Sepiad keels over, the Tharpod claws his way out of its mouth, raving about the horrors he's seen inside of the Sepiad.
The ending is is no slouch, either. Cronk and Zephyr finally make it down to Magnus after receiving aid from Lawrence, who proceeds to steal their ship, along with Dr. Nefarious. When someone raises the question as to how they're going to leave Magnus, Ratchet turns toward Ephemeris and promptly announces that he'll drive.
Right after that, we're treated to this exchange:
Clank: Ratchet! We cannot pilot a weaponized drone into Luminopolis!
There's a similar moment after the party defeats Commander Spog and Clank says that he knows someone who can fix the Commander if he's willing to help them. Qwark assumes that Clank is talking about him, and offers a line of dialogue that falls somewhere between CMoF and Brain Bleach material.
This leads to a hilarious moment; Qwark and Nefarious have something resembling a heart-to-heart which involves giving Qwark a wrench.
Qwark: An Inter-Galactic Tool of Justice Award!
The Plumber: If you boys are done, I'm gonna need that wrench back.
(Qwark and Nefarious stare at him)
Nefarious following the others into the Deadgrove because the elder Tharpod's bright pink creature creeped him out.
After Cronk and Zephyr do some research on Nevo and discover that he may have sold Dr. Croid's technology behind his back Cronk lets out this line:
Cronk: I detect copious amounts of whippersnapperism!
Die too many times around Ratchet?
Ratchet: You are such a noob.
Particularly hilarious if you're playing as him in single player. You hear him yelling, distressed, for Clank over and over... and then the above line completely blindsides you.
Nefarious figures out where Ephemeris is.
Ratchet: I'm impressed Nefarious. You did good. *offers fist*
Nefarious: *begrudgingly bumps fists*
Dr. Croid's amazing "translation" skills:
Ratchet:Do you understand what I'm saying?
Dr. Croid:I think he needs to poo! I'll go get a baggie.
*Cue Ratchet, Clank and Nefarious's faces of disgust*
Qwark:Hey Doc. Better make that two. Been a looong trip.
Normally, in Single-Player mode, if you play as Ratchet, Nefarious or Qwark, a CPU Clank will ride on your back like a backpack traditionally. However, if you play as Clank, Qwark will be your backpack instead.
Maybe it's the delivery, but this hammy line is always good for a laugh.
Qwark: For our own survival, and for drama, we must set aside our petty squabbles and act together as a singular unit!
The team discovers Vac-Us.
Qwark: Hmm, a letter... (Gasps happily) And it's been written in macaroni! "Dear Lombax. These Vac-Us will come in handy. Love Susie."
(Qwark turns on a Vac-U, and ends up suctioning Nefarious to it!)
Nefarious:(Trying to pull himself free) Let me go, you half-wit!
Qwark: I'm trying! Maybe if I just- (Pushes button on Vac-U and sends Nefarious flying. Cringes as a loud crash offscreen occurs.)
The demonstration video for the Quantum Deflector points out that Qwark has been the target of many assassination attempts since his inauguration, and shows him being driven in his limousine and ducking under a bullet, throwing a Cartoon Bomb out from the back seat, and using his robot driver as a shield against a ninja.
Doctor Nefarious, of all people, destroying the Loki once and for all with a PIMP SLAP.