I think the key is well padded clothes, a good seat, proper adjustment.

For the seat I use a brooks, that I hand hammer in the sit bones area so I don't have to break it in.

I have fiberpile sewn into my torusers or shorts. It's pretty light stuff about 100 - 200. It's probably about the weight they make baby sweaters out of. The first time I was worried a seam would be in the wrong place, so I covered that with a second wider layer. This pair is super comfortable, and not only it is noticeably different in padding, but also as regards the adjustment of the seat height.

Seat position is really important, but for me it's less a flesh thing. I feel it in the nerves, or knees, and it's usually the kind of warning that can't be ignored. A nerve pressure in the crotch area is torture, think of the stocks, the rail and various forms of creative rocking of the victim, and needs immediate adjustment, and the knees can't be ignored either. Carry tools on your break-in rides to insure you have the right adjustment for all you needed layers.