I used to ride my Ducati Monster with clip-ons from Fort Riley, KS to Arlington, TX several times a year. It was my only mode of transportation. It wasn't the most comfortable ride ever, but it didn't hurt. I think I could ride longer on a CBR though.
One thing you have to learn to do is use your waist to hold you up. You shouldnt support yourself with your wrists. Once you et up to speed the air will hold you up so it can be pretty comfortable. My biggest complaint was that my ass hurt after a long ride. 
I have read about people having numb wrists with some bikes, and they say that heavy bar ends and gel grips will usually take care of that problem.
I rode out to and back from western MA on Tuesday afternoon on my Hayabusa to see what I would feel like after 200 miles. It becomes pretty standard practice after a bit to not load your body weight on your hands when riding in what is basically a fetal position, and I can keep my balance using my knees and feet. Additionally, my gut is sufficient to engage the tank, if I'm seated close to it, and that helps as well. It wasn't bad to do the 200, and it went by without any discomfort to speak of. I found that there is enough seat room to get a couple of positions out of, even though there's not really anywhere to move your feet to. ( I miss the days when passenger pegs were at the same vertical level as the riders, like on the cb's). My right wrist did get a little numb at one point but it was pretty simple to move my hand around and still maintain the throttle setting. If I had remembered to put a throttle rocker on and wear ear plugs, I would have been fine.
The bad thing about the sport bike seating position for me, is lateral visibility, I'm used to looking over my left shoulder at intersections where the oncoming traffic is at an acute(less than 90 degree) angle, and now I have to strain to see what's coming at me.
There are all sorts of bar risers and adjustable foot pegs to help you find a more comfortable seating position on the new crotch rockets, and I know a lot of folks have used them with good results. I didn't have any residual shoulder or neck aches following the ride, and I'm pretty sure I can go a couple of hundred more miles in a day if needed. However, after riding the Yamaha FJR and the Concours 14, I'd go with one of those bikes if I was doing big mileage regularly. Because you are more upright, it's easier to see the scenery.