My major upright bike experience is on my bakfiets. So that's heavy as can be, to which I attribute some of my knee pain. But, I definitely have knee pain if I'm taking it for a longer ride, especially when it's loaded with kids and groceries. The seat height seems to be important though. It goes between my 5'6" wife and me at 6'2", and when I'm not thoughtful about resetting the seat well, I hurt more.

On the plus side, with the bakfiets, we're usually stopping all the time for errands, to play, to talk with friends... so I never seem to just ride it straight for 10+ miles.