For me, I would have to say dropping Encore. I don't know what was going on through his little drug influenced mind, but I'm pretty sure his friends (D12, Dre) could have convinced him to not release the album.
Another one (not so big) was having the whole gangster phase. It just didn't fit him, and once again I don't see why his friends didn't intervene.
What bout ya'llllll?