There's huge amounts of trial and error involved, but I can only say what what has worked for me. I switched to the upright position because it is much easier on my backside and groin. I get some really nasty numbness if I stay in a crouch too long. A good wide flat bar on a well-fitted bike gives you a lot of room to vary your posture, and by far the biggest enemy of long-distance riders is pressure and fatigue caused by staying in the same position for too long. If nothing else, just stand on the bike periodically while riding to take off the pressure every so often. I wear regular gym shorts when I ride and there's no special padding on my saddle and I can honestly say I never have any serious backside pain or problems after a long ride. Conditioning might be a factor here. I've found that the butt muscles become their own padding as they develop.

The hand issues I've had have related to doing a bunch of centuries on a too small bike and initially without gloves. I got a well-fitted FX3 a few weeks ago and started wearing padded gloves a couple months back. The FX3 has a great handlebar setup that really protects your hands from bumps and gives you some nice hand position options. Also, the carbon fork is a great shock absorber. All I can say is that after 218 miles this last weekend and 205 the weekend before, I'm not having hand problems anymore.