When I was at a loss getting my 10sp Shimano RD to shift nicely (7800 shifter, 6600 RD, stock Shimano cables), I wondered if it was the derailleur hanger.

Rode it to a shop, had the guy check it, and yup, that's what it was. Fixed it, rode home and it's been sweet ever since (more than a year now).

Nobody's said to check the hanger yet, so just throwing that in here.