DearS, MM and possibly DN Angel.
Good anime I never hear anyone ever mention.
Mad Masochist is an awesome anime!
Is Serial Experiments Lain obscure?
I think this one has entered the realm of obscurity as it's a bit of an older one now, but it's definitely another great one.
These are some anime most people I talk to have never heard of:
Hanbun no Tsuki ga Noboru Sora
Foton (AKA Photon: The Idiot Adventures)
Ayakashi (Not to be confused with Ayakashi - Samurai Horror Tales)
Vampire Princess Miyu
Kaze Makase Tuskikage Ran
Fractale
Red Garden
Paranoia Agent
Are we including movies?
Night On The Galactic Railway
The Day The Earth Moved
Piano no Mori
Kaze wo Mita Shounen
Dead Leaves
Yeah, I have a bit too much free time these days...