After Effects CS4 and Windows Vista 64-bit do not get along well. Although my newish computer renders my projects over 60 times faster than my old one did, the interface has always been somewhat sluggish. My most recent project made significant use of the Vector Paint effect, which served to highlight the problem. The paint tool was very hesitant, and it crashed frequently. Quite a bit of hunting around on various support forums revealed a solution: Run After Effects in XP compatibility mode. My interface is now very responsive, and Vector Paint works flawlessly.
So there you go. I haven't yet encountered any drawbacks, but I'll post an update if I do.