And don't hook it into that awful InterNet, and don't attach any portable media or enable any modems... better yet, don't even turn it on.
Actually, I've gotten where I LOVE Malwarebytes.. it's made me quite a bit of pocket change recently from folks that don't practice safe hex.
Remember going with Malwarebytes after it got rid of a nasty malware that hijacked my desktop, while the other anti-spyware programs kept on brutally destroying suspicious cookies for me but not the hijacker.
Using a combination of Avira AntiVir and Malwarebytes.
Nothing. And I mean *nothing*. No antivirus, no other placebo "I will make your PC 10% faster and more secure" crap (in reality, every additional software running will make the computer slower).
It's all a matter of knowledge and how one is using a computer. After a clean boot, my Win 8 uses around 500MB RAM, with 23 (or so) processes running. Clean, fast, simple. I don't like to spend hundreds on hardware only to waste all the resources with useless background crap.
There are basically only two things I do every now and then:
a) defragmenting the system partition
b) cleaning up, compacting and defragmenting the registry.
I keep a image of my installation for my windows machine with everything set up as I want, updating the image I save every year or so for updates/service packs etc. I have NEVER had a virus I use Firefox with No Script, AdBlock Plus and DoNotTrackMe addons for all browsing. I don't understand how anyone with a comparable level of IT skills would get a virus in the first place, they should know better.