Every season, the folks at Supernatural bring us a big bad that the brothers usually defeat by the end of the season. First it was the Yellow Eyes Demon, then Sam and his powers, the devil, Bad Castiel and finally Dick Roman.
With Dean being stuck in purgatory with every type of demon that ever existed, it leaves the writers open to pick a doozy. My guess is when Dean and Cas find their way back that something's going to come through with them. It may even be IN Dean.
Crowley could be the big bad this season as well. The lead in hell just took the prophet and who knows what his plans are for that. I know it can't be good. Crowley has an agenda, but where do you go when you're the leader of hell? Will he try to take over the Earth or heaven? That doesn't seem like his style.
The vampire Alpha is still alive and there is still a ton of mythology out there they haven't even touched on. If you want to be honest, I hope they go in a completely different direction. The first season, as we were getting to know the brothers, was a creature-of-the-week year.
I think we and the brothers have lost touch with who they really are, and it's time to get back to basics. I would rather have a season where we see the brother get closer again and play off each other. The show used to be funny and have some heart, but that's all changed. Everyone is so angry and disillusioned after everything that has happened.