On my road bike my saddle is canted slightly up. Bear in mind my handlebars are at the same height as my saddle. On our tandem my saddle is tilted slightly down - handlebars are lower. All of my weight seems to be on my sit bones. Both saddles are all the way back on the rails. My knees like it that way. Could it be that your shorts are irritating that area. If I wear certain jeans to work (I commute on my bike) I sometimes have a similar problem. Now I just don't wear those, unless I'm driving.

V.