Without the patch or an earlier hotfix, you can quicksave when dead, which could end or setback your game if you are mostly relying on the single quicksave (the patch adds 2 quick saves by default, which you can increase if you wish).
There was a bug with removing an item with a Magic Barrier bonus if you had not otherwise learned that skill, which could cause your resistances to eventually drop dramatically (so any elemental attack would be a one hit kill).
Before the patch Finnigan's magic lockpicks were breakable, and weapon expertise with a fixed range bonus, rather than percent, were broke.
There are a couple main plot quests that you can break without the patch, but there are fixes for them. Don't start killing friendly NPCs or toss a teleporter stone into the castle before getting an invitation and you shouldn't run into any major problems.
QUESTBREAKERS AND MAKING DIV LIFE DIFFICULT - the majority of problems have a fix, or were fixed in the patch
