No, not a post concerning the inimitable Linkara - though his comic-based webseries is awesome and I urge any fans of the medium to check it out.
Anyway, I was recently thinking about the use of fourth wall-breaking comedy in comics and animation, and how there's only so much of it I can take before it becomes annoying. Moments where the characters directly address the audience, refer to their artificial surroundings, or otherwise step out of their role and remind the viewer that what they're watching is not real, can be very funny if it's done right and very annoying if it's done wrong. The old Looney Tunes cartoons always seemed to get it right, because they never took themselves seriously. When Bugs Bunny cuts the film at the end of "Rabbit Punch" to get out of his predicament, or Yosemite Sam threatens to shoot a guy in the audience in "Rabbit Every Monday", or when Daffy Duck flusters with his sadistic animator all throughout "Duck Amuck", nobody gets taken out of the story because the whole thing is in the spirit of fun. There's no complex narrative there, it's just gag after gag.
But when there's an actual attempt at a real story going on, a fourth-wall gag feels out of place to me. The American dub of "Pokémon" has had a long history of doing this - stuff like Meowth pointing out that he wasn't drawn with a nose in "Pokémon Scent-sation" or Jessie rationalizing her padding-filled plot with the offhand remark of "We have to fill a half-hour" in "Hypno's Naptime" just comes out of nowhere and rubs me the wrong way. (For the record, the Japanese version of "Pokémon" takes itself a little more seriously and generally doesn't do stuff like this.)
Basically what it boils down to is that fourth wall humor works best when there's no real focus on story, or when the show or whatever in question is going strictly for laughs. I rarely use fourth wall humor when I'm telling a story because I want my readers to feel that my characters and their situations are real; having them turn to the reader and say "Ridiculous, isn't it?" would ruin that illusion. That's why I don't do any fourth wall gags in "Forever 16" - those characters feel very real to me, and I hope to elicit that same reaction from my audience.