I use Kaspersky Anti Virus always resident, Mbam paid version (but I do NOT run it resident) for occasional on-demand scanning once a month or so, Spyware Blaster (it helps protect against known malicious websites - you have to update it manually every week or two if you use the free version) and WinPatrol (paid version)
Most important however is smart computing - don't visit questionable websites, don't download anything unless you are certain you know what it is and that it is safe (the same with opening email attachments), don't let anyone else use your computer - at least not your admin account or your primary user account, etc.