I recently started getting a twinge in my left knee, not painful, but noticeable. I rotated my cleats on both shoes to pull my heels in a just a wee bit so that when the shoes are clipped in they are as close to parallel with the bike as I can get them. Bada-Bing, no more twinge.

My knees also give me trouble if my seat is too low.

My pedals are Look A5.1 with adjustable float that I keep set on zero.

This worked for me. If you're having pain, and can't get it adjusted out, take it easy on the strenuous rides and see a Doc. Knees are something you don't want to mess up.