The longer any given conversation involving Xander Crewes goes, the more likely it is to reach Crowning Moment status, as his understanding of whatever's going on declines but his anger/confusion/excitement/whatever increases. His exchanges with Killface deserve special mention, particularly in season 2.
Almost the entire episode in which the Xtacles attempt to pass Nearl off as Xander Crews, with the highlight being either "Elephant showers with their noses!", "It's complicated enough without all the evil twin bullshit having," or the entire Flowers For Algernon/Harrison Bergeron/Tom Bergeron/Agamemnon exchange.
Late in Season 1, pretty much everyone (most notably Taquil and a group of extremely drunk Xtacles) end up in Chinatown watching a deathmatch. Their commentary is consistently hilarious, but special mention goes to Taquil's repeated proclamations of "Man, I love Chinatown!" or "I hate Chinatown!"
From the Season 1 finale: "My parents never established boundaries!"
Xander's "gray market safaris" and his claim of a mama panda bear being "the most dangerous game."
When Xander and Killface finale make it to the debate, poor Carter Hawkins (the moderator) is subjected to absolute chaos as the two of them try to orient themselves, with Xander shouting things like "Why does he get a spirit animal?!" and "I think my buzzer's broken!"
Near the end of Season 2, Wendel's digression on the morality of his plan: "We're dealing with some pretty profound ideologies here. You know, on the one hand, there's anti-abortion. On the other hand: Jengo! I've got a machete! Deal with it, Congress. You can't legislate morality. Although you can legislate machetes, turns out."