For me, it depends on the brand of the weapon. Ruger single-sixes, while extremely popular and accurate enough for most needs, they are not as accurate as Ruger's autos. Accuracy ain't everything on the trail, but if I want a squirrel perched on a limb 40 yards away, I can get him with my Mark III.
That said, Smith's L frame revolvers are without equal for accuracy and dependability. But the majority of single action .22's are just not up to real accuracy that one might want beyond 20 or 25 yards. Other brands come to mind, but Smith and Ruger are on top of the list, IMO.
Regarding the interchangeable cylinders of the single-six, we have to consider that a .22 LR and a .22 Magnum are not exatly the same caliber. The Magnum is ever so slightly larger, which makes the LR a little bit loose as it travels the length of the barrel. If I had one, I'd use Magnums exclusively, which sort of takes away from the usability of the LR, the woodsmans's friend for ages past. It's my useless opinion that one should chose the most accurate .22 he can afford, and to me, that means a Mark III or a Smith revolver.