I can save games in blood, but once I exit out of the game and then go back later to load it it up, it's gone. Any ideas? I'm playing on a Vista 64 bit quad core machine with an ATI Radeon 3200
EDIT:
Also forgot to add it won't save any changes I make to setting like changing the screen size either.

Hmm.
Maybe you need to set it to run as administrator in compatibility mode?
Vista and Windows 7 add additional protection to anything installed into the Program Files folders.
I'm running both Blood and Blood 2 under Vista 64, and am able to save end load games without any problem.