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Count me worried too :( Many (most) people assume Jensen's referring to Crowley or Castiel, but I think this could be a red herring, and deliberate obfuscation on his side. As long as we don't get the fratricide scenario, I'll accept any 'fan favorite' dying. But I fear that's exactly what's gonna happen. But if they do go down that (predictable) route, I think I've reached the end of my patience with this show, regardless of its execution and how they plan to bring whoever dies back.
Having said that, I think Sam killing Dean could work as a twist on the expected scenario, but Dean killing Sam, thus fulfilling the prophecy (when pretty much the entire show has been about him resisting that fate) would just be the final straw for me. I just don't trust the writer's (i.e. Carver) skills to pull it off in a satisfactory way. It's a line I hope they won't cross, but from the reports I'm seeing and hearing I'm not optimistic. This is one occasion when I wish my cynicism turns out to be wrong.
Jensen volunteered during his lounge, when asked about giving us a minor spoiler, that another fan favourite will die, and that he has no idea how the writers are going to dig themselves out of that one.
Count me worried now.