This is a tough one...although my opinion varies greatly based on what I'm watching or what's going on, or just my mood, I'd have to say it's between one of these three (no particular order)...
1.) Elfen Lied -
What can I say? I love a good romantic tragedy! Also one of the few series that I can literally sit and watch again and again and never grow tired of. The story is great, and of course, me being a red-blooded male, I enjoy me some good violence and boobs anyday. ;P
The manga version of this is also amazing, albeit the ending, while more fitting to the series, is far sadder. :'(
(though don't get me started on talking about how much I had Yuka...most annoying anime character...EVER...though I suppose that was supposed to be her point ;P ).
2.) Black Lagoon -
Another good anime with a fairly dark story. Again confirming that I am one crazy bastard with a weakness for slightly crazy women. ;P
Episode 7 alone I have to honestly say is probably one of the best episodes of any anime I have ever seen. (The scene where they are watching p*rn in particular was freaking hilarious!)
This series is also, oddly enough, the best english dub I've ever seen hands down. I have to applaud the dubbers in that they didn't tone down the language or censor it at all (because we all know how foul mouthed Revy can be ;P ).
This is by far the series I'm most excited about seeing continued, as both the manga and novels are amazing...must...watch...season 3... *twitch* -.0
3.) Fullmetal Alchemist (and Fullmetal Alchemist:Brotherhood) -
Yes, I realize these are *technically* two different series, though they are both up there in being amazing. I have enjoyed both versions of the anime, they have done an amazing job on both versions.
I have to give FMA the credit it deserves, I still think that this show (and parhaps maybe Death Note) is the only "main stream" anime that deserves all the credit it gets, it's just that amazing.
Best characters designs I've seen in any anime ever!
4.) FLCL (or FuRiCuRi, or FoolyCooly ... whatever the hell ya wanna call it ;P)
An old series, but still one of my all time favorites, as I'm sure some of you have heard me harp. ;P
I'm still annoyed to this day I don't own a legal copy of it, as it is out of print :'( ...but this show is a must watch for anyone who ever wants to call themselves a true anime fan.
Best part? This show is really as crazy as people say it is...it's the kind of show you can watch over 30 times (believe me, I have ;P) and STILL see something new each time!
5.) Dragonball -
Please note...
I said DRAGONBALL!
NOT DBZ, DBGT, or DBWhateverTheF*ckElse!
Dragonball, plan and simple, is by far one of the best shounen classics ever made. Hell, you'd be hard pressed to find a shounen series out today that doesn't on at least some level pay homage or draw from this series.
It really is that good.
From amazing character designs, to a plot that is pretty much known by almost anyone, anime fan or otherwise, it really is a much watch for any anime fan.
Heh...this list was actually a little harder for me to write than it looks, I have too many shows that I just absolutely love to death that didn't even make it up here, it's that hard a pick.
Lord knows my manga list would be very different as well... (don't even get me started, I read FAR more manga than I watch anime ;P )... but enough rambling, that's my 2 cents ;P