NY, I suspect the knees are from 2 things: The amount of lunges, squats, jumping I do 2X weekly at the gym comboned with using the compact. My Guru has the same compact gearing +1 lower cog as my new bike. I also noticed the knee issue when I first started riding the Guru, and it still happened when I switched back and forth from the bike with the triple. But, not as much, over time. I just have to keep telling myself using the small ring on the compact is not the same as the granny on a triple (which I have no issue using!). You have to use the small ring on the compact a lot more, there's a lot more switching back and forth. My sweet spot with the compact gearing is a combo that is just a teeny bit cross chained; hence I try to use the next one up, which is harder than I am used to. Hopefully, I'll get used to it, since now this is all I have.
I've been using Speedplay Xs for 10 years. I had SPDs on my first road bike and switched over when I got the Trek 5200 in 2004. I have Speedplay Frogs on my Guru, so lots of float on both bikes. My sense is if I stopped the stuff at the gym, the knees would not hurt, but really, I am not doing that much there and just with baby type weights of 6-16 pounds. I just have to get my body used to it. It's not pain, just achiness around the outside of the kneecap from the medial point, around almost the whole way, but not on the top.