Here is a new product that is in beta at present. It looks as if it might fit into a layered approach?
Seems to be based on heuristics and behavioural analysis.
http://www.threatfire.com/faqs/
This product used to be known as cyberhawk.
And here is one for the toolbox?............... it doesn't need installation.
http://www.mwti.net/products/mwav/mwav.asp
Free/free for private use