For me it depends on what type of riding I'm doing. For example there are routes that I take near me where I can go out for 2.5 - 4 hours that cover somewhere between 35 - 45 miles. These rides have a good handful of hills to climb as well as flat sections. In this case getting out of the saddle, changing positions on the bike (in the drops, hoods etc.) and generally having to do different things prevent it. On the other hand some charity rides that are 75 miles of completely flat I have more body parts that are in pain after 40 miles of flat only than anything else. I also have a favorite pair of shorts that I depend on and I make sure I wear them on the long rides.