Ad-Aware and Spybot together can catch most stuff but if it's firmly entrenched and you don't have the knowledge to dig the registry and identify running processes catching some of the tricker ones (start two processes, kill one the other restarts it and other tricks) can be next to impossible.
A clean start, a copy of both run regularly and a copy of Firefox or Opera is probably the most effective option but the most work. Popups are annoying and are probably being caused by spyware on your machine rather than websites, if you do choose to continue to use IE, disable ActiveX, that's where most of the really icky stuff comes from.
buying a mac works too
