You'd think they would be sick of it by now. Why not try something original? Have them be space pirates in an alternate dimension or something. Dying in Supernatural is so 2008.
If they do die, I don't think that would rule out a mini-series. Death in Supernatural is more of a suggestion than a rule really. It can be reversed it they want it badly enough. And they don't REALLY need Castiel if they make a sequel movie. I'm sure they could make up some alternate timeline version of Cas for Misha to play if the fans whine loud enough.