There is only 1 thing I fear that could possibly go wrong and hurt the game,and I wish it won't be the case.
Random crashes.
Honestly,the single thing that annoyed me much while playing Oblivion and Fallout 3 was that at some random points the game would crash to desktop with no apparent reason. At xbox360 the game freezed instead of showing up the desktop screen.
That's the only thing I think can possibly go wrong,so I please Bethesda to make so that's not the case with Skyrim.
If I remember correct,the games had this problem because they had a bad way to use the RAM of a system,and it was because of Gamebryo.
I think that since the engine is going to be a new one,there won't be the same case.
But that's my only fear for a game I know that in every other way is going to be excellent!