Such a glorious episode, isn't it, and fraught with Winchester brother angst. It's also, I think, the first episode since "Wendigo" that puts emphasis on all that rage that is at times central to Sam's character. And unless if you count "Bloody Mary", it's also the first time that we're shown a...shall we say, darker Sam, or at least a Sam that is lacking his empathy filter, which is also something we'll see rear its head again, particularly in season 6.
This episode, I'll state for the record, was written by Richard Hatem, and this is the last episode that he'll write for Supernatural. He also wrote "Phantom Traveler", and it's interesting to me that both of his episodes carried themes of possession in them. Hmm. ( "Let me know if you see any dead people, Haley Joel." )