I use Adaware spyware and Avast Antivirus (Although It has never found a virus on my comp....maybe a good thing!). I cant get on with firewalls, sick of them blocking usefull stuff...unless somebody can recommend one that's more user freindly? I also recommend the Mozilla suit: Firefox Web browser and Thunderbird email.
Just a side point!
It's worth considering formating your hard drive at least once a year. This then gives you a nice clean start to get things rolling again, and gets rid of those thousands of unnecessary files that microsoft loves keeping! Obviously don't do this unless you're hundred percent sure/confident you can reinstall windows and all the drivers! It's the ultimate fix all though!!!
I also have a second harddrive fitted, which is used for backup only. Don't know how I managed without it!