This may sound trite, but I use a few simple and free pieces of software that works so great together, I couldn't imagine running without them.
1- Zone Alarm which blocks all my ports.
2- AVG anti-virus that works so silently I'm not even bothered with alerts anymore.
3- Web Washer by Siemens which stops popups, popunders and everything else.
When I download, I use Fresh Download accelerator - also free, and I set it up to use my AVG to automaticaly scan everything the moment it finishes.
Then once a week I do a complete scan with AVG and Swat It - a Trojan and Bot killer, oftener if I suspect something, then I do spot checks on those files.
So far, I have found nothing virus related and I used to surf the net like a madman.
I use AdAware, Spybot, after I have visited any web site that requires info, and always seem to find Alexa which i immediately remove.
So, in the end, it pays to be vigilant and resist the temptation to open that "iffy" Email.