I use the standard Spybot/Ad-Aware combo,
AVG Antivirus (free for personal use), and my own manual registry hacking.
The Google Toolbar works wonders for pop-ups in IE, but I use Mozilla Firefox for everyday browsing, only opening IE for Windows updates, or the rare site Firefox won't render properly.
I must say though, that spyware/adware/crapware is becoming more of a problem than viruses. I work for a small computer repair shop, and well over 80% of the problems we fix are directly caused by this stuff- pop-ups, slow computers, even corrupt winsock files and registry entries (resulting in loss of internet connection).
I think the biggest things they come with are the file sharing programs like Kazaa, LimeWire, iMesh, etc. Lots come from fake banner ads and pop-ups posing as Windows system messages (with messages like "your clock is not set" and "if this is flashing you have ______") people unwittingly click on. What's worse is that many are accompanied by downloader trojans, so once you get one, within a few weeks you'll end up with a bunch more.
You know it's a sad world when people try (and succeed) making money by hijacking your personal property for their malicious use (either as a spam relay, or constantly producing advertising pop-ups). Makes me very happy to be part of FIRST, with the hopes that within a few generations, Gracious Professionalism will work it's way up the corporate ladder and this sort of thing will be frowned upon by the supporters of this type of marketing.