I would say Kaspersky Anti-Virus
I used Norton antivirus (2002, 2003, 2004 and 2005) for more than 5 years and to be honest it's a good program. One day my PC was hit with a virus that norton could only catch and couldn't delete and it kept annoying me with its pop-up alert window every while.
Norton had an upper hand over other programs due to its live-update feature, but currently almost every antivirus has that.
Kaspersky virus definition is updated every a few minutes without interrupting your work, and in case a new virus (or worm) is found, you can inform them and within 2-3 days they release a new virus definition.