"Once Upon A Toon", no question. How does MAD celebrate Cartoon Network's 20th birthday? With a character from pretty much every classic show uniting onceagain! Including Johnny Bravo, Dexter, Samurai Jack, Blossom, even Numbuh 1, and most of the time Cartoon Network just pretended KND didn't exist!
Even better, Dee Dee's Overly Long Gag about showing a "sample" of MADon a TV, in a recursive, matrioska-esque way further hammers down the point about how MAD's pop-cultural nature is the only way the characters could possibly have been acknowledged and gathered. As a Youtube commenter pointed out, this is 50% Biting-the-Hand Humor, and (much more subtly) 50% fan-trolling. And 100% awesome.
Rio-A: Rio gains Green Lantern powers, and gives rings to other flightless birds (Mordecai, Big Bird, etc.) to save Jewel. Awesome way to kick of Season 2.
The Fandom Nod in "My Little War Horse" with the cake that has "Go Bronies" on it.
Speaking of starting off season four with a boom (or should we say, a sonic rainboom?), MAD co-aired that sketch with "Rainbow Dashand Bernstein, a definite CMOA for the brony community. While the Fandom Nod in "My Little War Horse" was awesome and the other sketches never made fun of it, this sketch centered around MLP's male community in a positive light. But this line shows MAD has done their research:
Rainbow Dash: ...I can show you how to be 20% cooler by being a brony!
There's also the part where he was fighting dinosaurs.
MAD's parody of The Morton Downey Jr Show (Issue #286, April 1989), called "The Moron Downer Jr. Show" deserves a mention. In the end of the parody, the Pope himself visits the show to deliver a message. The comic ended with a full page splash of the Pope punching Morton in the teeth. Damn!