- Slow read/write disk access up to 15-fold
- Definitions may not be available until after a virus has reached your computer
- Deleting or quarantining false positives can be hazardous
- Background scanning can interfere with software installation and updating, leading to malfunction that is difficult to correct
- Popular free software like AVG updates only daily, so even if proper definitions are available, your software might not have them
- Marketing preys on fears of the Internet that aren't proportional to the actual risk involved
- The same files may be scanned many times even though they hadn't changed at all since the last scan
- Hazardous files may still go undetected by scanner incompetence or bad virus definitions
Beyond this, it's wise to use an active firewall such as the one the comes with Windows XP SP2 or Vista, preventative steps such as subscriptions against malware sites as is provided with SpywareBlaster and AdBlock Plus, and to keep unnecessary networking functions disabled.
UPDATE: Avast is free, has frequent updates, and can be set to only scan when files are being copied/modified. I now prefer this approach over Orbit Downloader + ClamWin.