Depends on the road. If it's boring straight/flat/interstate riding, I get about 40 miles before I get uncomfortable, at 80 miles I can't think about anything but the next stop, at 120 I'm shifting from one side of the seat to the other to give one cheek a break. And, if I get through a whole tank of gas, at about 170 -180 miles I need a crane to pick me up and stretch me out. And nothing hurts more than getting back on the seat.
Twisties? I can ride them all day, a few hundred miles and not get uncomfortable. Tired, but not uncomfortable.