After much trial and error at experimenting with different anti-virus and anti-spyware applications, I have this setup.
Microsoft Security Essentials (MSE).
http://www.microsoft.com/security_essentials/
Malwarebytes AntiMalware (MBAM).
http://filehippo.com/download_malwarebytes_anti_malware
WOT for safe web browsing (no conflicts with other software nor slows down my browser).
http://www.mywot.com/
MSE is lightweight, leaves a small footprint, has a very low level of false/positives readings, doesn't kill you with annoying prompts and is basically a set it and forget program.
MBAM I use as a compliment to MSE and has become the standard today at malware detection and removal. Run MBAM at least once a week and anytime you may have suspicious files. Always update before scanning.
WOT to which I previously spoke on, is a great tool for determining whether to click into a bad website and getting hit with malware. More of a preventive tool.
The first and foremost preventive measures one can take is to always use safe browsing practices. An ounce of prevention is worth more than a pound of cure, anyday.
Stay safe.
Cheers...gwb56