I can't even imagine Thanos being the villian. Wouldnt most of the movie have to be in outer space? And what about Adam Warlock, and Silver Surfer, they would have to be in it, and the Fantastic Four. I just dont know. You think he'll have the infinty gauntlet?
I think that if Thanos were to land on Earth and setup shot (think what Daredevil did with the Hand in Shadowland) it could work. Given the lack of any real plan in the first Avengers movie besides "let's run around fighting people in the streets" I suppose a large portion of the movie would be the Avengers trying to fight through defenses and storm the castle. If you wanted something for the lightweights to do, send them after infinity gems. Surely, that would be why Thanos is on Earth, to collect the gems that are hidden there? It would make for a fast paced movie.