I would say Avast + MBAM + Sandboxie.
Sandboxie is good.
When ever i download stuff i always put it to sandbox for observation.
IE, FF, Chrome, PDF reader, DVD drive, F drive which is for USB flash drive is automatically run by sandboxie.
Btw! as of now i remove FF and IE in sandboxie because of browser crashing which i created a thread.
http://forum.avast.com/index.php?topic=72404.0