3. Crowley
He just wont die or go away. Crowley has been an antagonist that has lasted a surprisingly long time for a show that boasts an important antagonists maximum life span at 2 seasons. We cant really complain though because he is a very interesting and devious character that will stop at nothing to accomplish whats on his agenda. As mentioned before, the gates of hell will be a main focus and goal of the Winchester brothers and Im sure Crowley will be more than willing to finally kill them over that. From a cross roads demon to the devil himself, Crowley has become a powerful foe and will certainly prove to be a great antagonist for the next couple of seasons simply because he is a thorn in the brothers side, one they cant seem to pull out.