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Depends on the genre.

Shonen/action anime: I'll go for Sorcerous Stabber Orphen, Negima, Bleach and World's Strongest Disciple Kenichi.

Sports: Captain Tsubasa and Slam Dunk. Manga, there's Fantasista and Area's Knight... Oh, and Ice Revolution. Haven't read much of that one yet (damn scanlators,) but what I've read, I've enjoyed.

Magical girls: Sailor Moon, Powerpuff Girls Z, Corrector Yui and Tokyo Mew Mew (NOT the dubs, for any of those.)

Shoujo: Kimagure Orange Road, Karin and the mangas Skip Beat and As The Death God Dictates.

Historical anime: Rurouni Kenshin wins, followed close by the not-so-historically accurate Sakura Taisen/Sakura Wars. Manga mention to Ravages of Time, a manga for those who are already knee-deep into the Romance of the Three Kingdoms sagas.

Futuristic anime: Appleseed/Appleseed Ex Machina, and Armitage III PolyMatrix/Dual Matrix.

Mecha shows:Top place is for B't X, followed close by Zentrix and old good Macross (not Robotech.)

Psichological anime: First and foremost, Perfect Blue. One hell of a disturbing movie. Second-best is Evangelion (even though I hate the main guy's lack of guts,) and there's a manga that, if it has an anime, may go into the first place: Doubt.

I am of the mind that anyone who has only one favorite per genre, or even one favorite, hasn't seen enough manga and anime yet. I could list all the anime I've watched more than twenty episodes of, but I don't think the forums can take on such a long list without breaking. ninja So, really, picking ONE anime as my all-around favorite? I simply can't.