Sayonara Zetsubou Sensei (So Long, Despair Teacher) is irreverent, sarcastic and crammed with anime in-jokes and otaku references.
What I like the most is the old-style nostalgia that the series unashamedly uses, especially in the title cards and the kanji. Another subversion there!
Try the first 8 minutes of the first episode on Youtube:
The reference to Osamu Dazai in the Episode 3 opening cracked me up.
The Episode 4 opening. NSFW (some disturbing bits), but graphically brilliant.