Y: The Last Man has two issues that focus on a theatre group trying to make important work about the post-Gendercide world. Their first effort is not received well. Later they try films and comics. Also, a supermodel whose profession is obsolete and is now clearing bodies (a minor character from early in the story) gets a issue later on.
Peter David, fed up with the Wolverine Publicity that drives the X-Men franchise, once wrote an issue in his X-Factor featuring none of the usual cast, instead focusing on popular characters like Wolverine and Cable.
In a similar vein, Walt Simonson wrote a three-issue Fantastic Four arc(with art by Arthur Adams) in which the FF are temporarily replaced by the four most over-exposed(during the 90s) characters in the MU: Wolverine, Hulk(during his gray-skinned Mr. Fixit phase), Spider-Man and Ghost Rider.
The classic Uncanny X-Men story Kitty's Fairy Tale. The cover even featured Kitty Pryde announcing, "And now for something completely different!"
Strangers in Paradise had a Superhero Episode, as well as a send-up of Xena: Warrior Princess, after it was pointed out by fans that Francine and Katchoo resembled Xena and Gabrielle. (Katchoo was less than thrilled to wind up as Gabrielle.)
Adam Warren started the last run of volume 2 of Gen 13 by doing a whole issue in the style of VH-1's Behind the Music, featuring each character's fake demise in ironic ways.
Issue #34 in both series of Marvel's "What If...?" were all-humor issues.
