I like to keep Windows on its own little drive for this reason. The only problems occur when I need to do major updates (Win7 SP1 comes to mind) where I have to set up boot order so the Windows disk comes first so it can pretend it is a unique and special snowflake and get on with installation.
Program Files is locked down nowadays, so any applications that try to write there end up going to VirtualStore or something like that in the Users folder. (I think. I don't actually use Windows that much.) But I agree with the sentiment, there are way too many places for data to hide.
"I think Michael is like litmus paper - he's always trying to learn." -- Elizabeth Taylor, absurd non-sequitir about Michael Jackson