Plot Stoppers
(Not a walkthrough like the other pages, but you need to know this stuff.)
"Doc, it breaks my game when I do this..."
Doctor: "Well, don't do that!"
(or download a saved game)
After you meet Raven upon exiting the dungeon, do not go back there until you have taken the Rune of Compassion to Raven at the ship. Whatever you left in Despise will have to wait until your return from Buccaneer's Den.
Katrina asks you to perform two side-quests. Either perform both quests before you leave for Ambrosia or wait with both until you return. Doing one before, and one after, makes it impossible for you to get the Crook of Humility without cheating.
There are three large demons on the island. They are supposed to be immortal but some Avatars have managed to nail one or more of them anyway (and messed up their game). Save them for later - let the plot unfold.
This bug only bites if you're using Patch 2. Shamino is supposed to help you locate the Isle of the Avatar but doesn't. The cure - Patch 3 - install before entering the Well of Souls.