I used 2x1 for a while under XP, and then upgraded to Vista. I immediately noticed stuttering in TF2, and realized it wasn't a video/CPU issue. I picked up another 2x2 for a total of 6GB (which I've been running to this day), and everything became nice and smooth again. Vista also absolutely flies with a lot of RAM, due to Superfetch keeping a lot of apps prefetched. Running 4 sticks didn't affect my OC at all, but then again, my FSB's only running at 333.
edit: TF2 isn't even a very memory hungry game. For instance, I had Crysis Warhead running a few minutes ago, and it was using something like 1.8GB RAM by itself. My total RAM usage according to task manager was a little bit over 4GB.