So maybe I'm missing something obvious here. I've got 12.1 installed now. I want to create an application profile for Skyrim. In the 3D Application Settings menu I chose the options I want. I clicked the save button. It opened a dialogue which was confusing at first until I read the help which said to go find the program the profile is going to be for. I navigated to TESV.EXE and clicked "Open" which is the only option other than "Cancel" on the dialogue box. Nothing happens at that point. No file is saved. No profile is created. No error messages come up. Nothing.
Have a look at the Gaming > Application Profiles section to see if anything has been added there. I've added a profile for Skyrim to get around an issue I'm getting on my system.
I'm using the 12.1 preview with two 5870's. Crossfire works fine and so far I have not had a single CTD or weird texture bug.
Not so great for the Mobility 5870s (which aren't really 5870s, just slightly down-clocked 5770s). All sorts of weird flickering effects, almost as if one of the cards isn't being given the data correctly. The main menu shows it nicely - the smoke renders just fine, but the Skyrim logo blinks like crazy. Hopefully this is fixed before the 12.1 WHQL release, because the 11.12 drivers don't contain the Skyrim Crossfire fix, and all the 11.11 drivers cause a nasty BSOD.