I'm a fairly heavy keyboard user, and now and then I experiment with new layouts and new techniques for improving my keyboard usage. Indeed, I began using the Dvorak layout many years ago.
Recently I've been revamping my emacs configuration, and realized that if I changed the location of the Control and Alt keys on my keyboard I could press them more easily with my thumbs, and even chord both keys together with a single thumb. Looking at my keyboard, I noticed that, on the left side, Alt is closest to the Spacebar and therefore the easiest to press with my left thumb. Next to it is the Windows key. On the right side of the keyboard, again Alt is closest to the Spacebar, with another Windows key right next to that.