Everything I mention here is free.
Adaware is another good freebie to run in addition to Spybot, most of the reliable download sites have this too, such as
www.download.com
AVG also has a free spyware tool but I've never tried it. ( free.grisoft.com )
HiJackThis might help you clean out some crapware from your registry if it uses your registry. CCleaner is a good registry cleaner too.
AVG was crapping out with my email tool (thunderbird which it should work with) so I've taken to running AVG manually once a week and using Threatfire for my resident protection. Threatfire is a heuristic scanner, not a signature based scanner like AVG, or the spyware tools. I've been pleased with it. The freeware isn't as good against viruses as the signature tools.The paid version is supposed be quite good.
All of the anti-virus tools are quirky when you run on-line games. Threatfire is a good solution for those who game on-line.
Further protection can be had, but they require some nerdy intervention.
NoScript for Firefox lets you pick and choose which sites run what scripts. Scripts are a common way to slip spyware into your computer. You can whitelist sites you visit frequently and temporarily allow scripts for one-off views and such. I wouldn't call it friendly for all users, but I've liked how it turns off lots of advertising crap too. Also lets me right click in sites that turn off right click as that's a script trick.
Lastly, Comodo Firewall. This is a good firewall, but when turned to paranoid mode, it gives very granular control of what's running on your computer. It pops up notices worse than Vista in this mode, but you have excellent control.
Phil