There's a lot to that question. I'd say Star Trek, which I love. But one problem I have with it... the tech level kind of takes the "space" out of the equation. I prefer shows like Babylon 5 and Firefly where space travel is dangerous all on it's own and the ships are more "Nina and Pinta" and less "Carnival: Triumph."
But, Firefly was too short. If Fox had let it continue I have no doubt it would be my favorite. And Babylon 5... exact opposite. It went on a little too long where it could have really ended with a bang and left the audience wanting more.
Twilight Zone... not always sci-fi. Carnivale... not exactly sci-fi. BSG (either of them) good but not really my favorite.
Most consistantly satisfying... I'd have to go with Dr. Who. It suffers from the "Star Trek" problem of too high a technology level to make space exploration dangerous enough, but it does fix that by including time travel and making that properly dangerous.
But I'd say my favorite sci-fi... has yet to be made. Firefly may have been it, good characters, great dialouge, dirty tin cans of spaceships as opposed to sterile floating houses, and fantastic worldbuilding and storytelling. If only it had been allowed to FINISH that story. Because I need to know how a story ends before I can call it "my favorite" or "the best." The reason that doesn't hurt Dr. Who... many Doctor's stories HAVE ended. And ended those chapters very well. They FEEL like endings and give closure. The new Doctor always feels like a new beginning.
So, probably Dr. Who. Although I'm looking forward to finding the show that beats it. Some Anime is right up there though. Outlaw Star, Cowboy Bebop, most recently for me Psycho-Pass (sci-fi dystopia through technology as opposed to space.) Anime question though. I'd like to get a good sci-fi anime going now that I'm done with Psycho Pass and Knights of Sidonia is on my Netflix cue. But I don't hear any buzz about it, is it any good at all?