Depending on era:
TOS - The Davids - love this design..
TMP - The Belmont - I love Ambassador variants on principle, but this is just sharp
TNG - The Armada - nothing says,"I'm going to kick you in the nuts till you puke" like the Armada does.
Favorite overall? I'm going to go with the TOS Davids, just because it'll probably otherwise be overlooked by the masses, and I think this really should get some mention.
honorable mention(!): The Rosa Class. Having the WWII inspired design fighting element (and Scrooge McDuck) is just awesome and completely original in Trek ships (afaik).