With Spybot, make sure you use the immunize function. In addition, if you switch the view to advanced, go to the Hosts section and the Spybot hosts lists. This will prevent your computer from accessing known bad sites.
You also need to have a firewall. Zonealarm is an excellent free one, although if you go for one of the pay versions it adds popup blocking, cookie control, and additional progam controls.
http://www.zonelabs.com/store/content/home.jsp
The free google toolbar will also block popups.