I have a 70L Osprey Aether, which is specifically designed to carry heavy/awkward loads for long distances over multiple days, and I have loaded that thing down for long hop outs. Like 2 gals of water, a 12 pack of beer, handle of vodka, and premade foods. I think at one point I was carrying like 80 lbs across portland/eugene. I had problems with my thighs and knees, but not anywhere where the pack was contacting me. Lots of padding and adjustable straps.
But then again, I've been firefighting and backpacking long distances in the wild for a long time before that, so it does have a lot to do with physical conditioning.
My first hitching trip I carried a 75L that was over 80 lbs. I soon learned, as others have pointed out, to drop shit along the way that I didnt need.