Took a road trip in both Prius & Prius C.... Only thing I found in my Prius is the thigh support after a while I had to stretch, I noticed I didn't have that feeling in the Prius C, but the C sadly does not have cruise control which would have helped a great deal. But both are fine... Prius road trip 420 miles... Prius C road trip 625.
Had an impromptu trip north. ~370 miles. Some lengthy uphill portions and my insistence at keeping the cruise at 75 dropped mileage into the 46 range. Ride back was a bit slower pace, up to 47. Didn't even stop once on the way home. Nice highway ride on the beaten pavement of I81. Cruise did do a good job of maintaining speed on inclines. With my old Civic the car would lag a few mph until it realized it needed to hit the gas, then it would often floor it. Prius was pretty fluid. Seat wasn't too bad. Ride up was good enough. On the ride back (rode up Saturday and back Sunday) my behind/tailbone and lower back had some rough stretches. Not sure if the back was attributable to accumulated seat time over two days or a non ideal night's sleep. For what it'd worth I'm a thin guy without much "cushion" back there, so the seat bottom could probably be a bit more cushy for me.
After having my Prius for about 3 months, the only thing I notice, that bothers me on long drives is the lack of padding on the driver's side arm rest. I'm one of those people that leaves his left leg bent and tends to lean it against the arm rest. Unfortunately, there's no padding there and after a couple of hours of my knee pressing into the hard arm rest, I give myself a rather painful indentation.
Drove from Southern Ontario to Orlando and back at beginning of April. Took three days going down to drive 2000 km (1,200 miles). Only challenge was getting used to higher speeds they drive in USA. As such, it wasn't a surprise to see several large accidents during our travels, so staying alert and well rested for long trips is essential. Prius worked very well for us, even on long steep hills through Pennsylvania. Fuel cost for trip was less than one airfare price (two of us travelling).