A very serious bug has been found with Shivering Isles that will render the game unplayable in many ways after about 50 to 120 hours of play (better FPS means bug hits earlier). The bug will occur regardless of whether you access SI content or not.

The bug is thoroughly confirmed on the PC. It is not known whether the bug affects Xbox users as well -- it is reasonable to assume that it would, but might not hit until around 150 hours of play assuming 30 FPS on Xbox.

While the situation appeared quite bad initially, a patch mod is now available for the PC and a tool is available to repair savegames that are affected by the bug or that are likely hit by it in the near future. Moreover, there is an official response from Bethesda:

Regarding the issue in which Form ID's are being used at a high rate in the Shivering Isles content; we are aware of the issue and we are currently looking into a solution. We appreciate your patience, especially from those of you affected by this issue, as we carefully work out a fix that will correct this problem without adding any new issues.

--NothingCatchy, Developer