I thought I would post this to hopefully help somebody else avoid the massive migraine I just got from attempting to install and run this game.
First of all, the game will not update from a DVD install. Just don't even try. The only version of the game I could get to update was the free trial.
There is some post from a CSR rep saying you cannot run this game under an admin acccount on vista. That's just wrong. I was able to finally get the stupid thing to run. I had to open the DDO folder under Program Files. Modify the dndclient.exe and dndlauncher.exe files to NOT run as admin and to run in XP SP 2 compatiblity mode and I was miraculously able to work. It's not enough to just check it on the main compatibility tab, but make sure you open up the 'settings for all users' and make sure nobody has admin checked there either. Installing on a couple different pcs had different default settings for all this.
Utterly amazing. This is the ONLY game that I had to purposely turn off admin privileges in order to get it to actually run.