Ok, so today I did a fresh install on an external drive to eliminate all possible variables and to see if it was an issue with upgrading from 10.5 to 10.6.
The very first thing I did after logging in was to set the mouse buttons up, test them, then log out and back in and sure enough, the buttons work fine when you set them up for the first time, but as soon as logging out, or rebooting, the problem pops right back up.
So for now, I think I may be patient, stick to USB Overdrive X, and hope (and pray) this is resolved in 10.6.1