From 2007-2009, a Canon 30D + 17-55mm f2.8 was in my bag. And from 2009-2010, the 5D Mark II + 24-105L or 35L was with me. You'd think that the difference between the 30D and 5D Mark II wouldn't be much, but to my shoulder, it definitely was. Either that, or carrying that load every day for a few years had a cumulative toll on my posture and alignment.
The increasing weight in the DSLR's was one of the reasons why I moved into rangefinders. I loved the Zeiss Ikon, but I also loved the convenience of digital, so the M9 replaced the 5D Mark II as my every day camera. Unfortunately, I've found that even the M9 and a couple of primes has been a bit much to carry, so I went to the Ricoh GXR, the Fuji X100, the Olympus EM-5, and now I've moved to the Ricoh GR and Panasonic LX7 as my daily cameras.
Perhaps in the future I will move to the Panasonic GM1 and a few small primes, perhaps the 14/2.5, 25/1.8 and 45/1.8. A far cry from the full frame DSLR I used to tote everywhere, but so much easier on the shoulder and bag.