I store all my personal data on redundant arrays and cloud storage, installed programs on a dedicated drive and the OS on another dedicated drive. This way I only have to wipe 1 or 2 drives and scan the raw data for threats. I also make a clonezilla backup of my OS drive this way the re-image only takes a short time rather than completing a long install process. Prepare for the worst and hope for the best.
Also, I only use MSE and occasionally scan with spybot, malwarebytes and a couple others. Anything more is overkill.... Careful browsing and clicking is the first line of defense.