To get rid of the low hanging fruit you can set an AV to do scheduled scans while you sleep. I use ClamWin for this (well I used to, before I stopped needing to put up with Windows). Honestly I've not had a virus problem using this, but it has more to do with browsing and download habits than any antivirus software. I absolutely abhor real time scanners and that crap, they just slow down your computers worse than a virus, and are generally just as annoying.
Install ClamWin and setup regular scans, use 7zip, never open Internet Explorer EVER, use AdBlock and HTTPS Everywhere, turn on "Click to run plugins", avoid Java, don't download sketchy stuff from sketchy places, investigate before you click, always install updates, never trust a popup.
These are the steps that have worked for me in the past. I've never had a problem with malware by adhering to these steps. I say never had a problem, because I never had a virus that was dumb enough to make itself obvious. It can be practically impossible for even forensic experts to recognize a lot of the stuff floating around out there, because once a rootkit gets running on your computer, it has the full capability to hide itself completely. It can change what the operating system reports for running programs, skip over itself when the disk is read, blank out its portion in memory, etc. Even before it is running, all it takes to avoid detection is to change a bit in the file, and hashes become invalid. Concatenate the server time with the file every time it gets downloaded, and you've defeated a huge fingerprint database. More sophisticated techniques for identifying malware are just as easily defeated.
[cools rant jets] But I digress...
Sorry, I just find most AV programs to be far too annoying. I agree with you actually. Especially if it doesn't bother you, it can be a good idea to run multiple AV/anti-malware programs. And YES! ALWAYS INSTALL THE UPDATES!! If I had a nickel for every time I saw someone else's computer begging them to install the updates, only to be ignored...
My point originally was that if you want to be sure you have no virus (beyond firmware/bios infections) you must wipe the drive. If you decide, well maybe it's okay to let one or two viruses survive, then that's your call and maybe avoid making credit card transactions and whatever else people do when they think they're safe. You might not even have a virus anyway.