I would agree that color and size are no where near as important as we tend to want to think. I would not go as far as Rob went though and say they make no difference. In my experience at certain times they do.
One example would be a few years ago on a remote fork of western Washington river. A buddy and I had hiked in to fish for the local resident rainbows when we stumbled across a pod of steelhead holding in this run. From a high vantage point you could observe both the fish and the presentation. First off came wakers and these resulted in not even a look. Next came wetfly swing with a purple spade type fly. Twice fish broke from their hold to charge the fly but when they got within a foot, they pulled up and returned to their holding position. Next came the same fly but in black. Three fish to hand. I know it is only anecdotal but I have to think there was something int eh black they liked better that day. FYI this was a sunny day with clear water conditions.
Another case was some years ago on a large Washington/Idaho river. The fish rolled behind a purple hotpants but did not take and would not come back. Next came a purple muddler but no interest. Finally a black hotpants was drifted over the lie and the fly disapeared in a perfect head and shoulders take.
Finally, Rob stated above that "The only time it makes sense to fish through a run more than once is to fish a radically different fly". Rob, I thought you stated above that size color and shape do not matter???
If there are aggressive fish in the run, fishing through it multiple times can be quite productive. Inland is right, the question should be what makes them aggressive? Sometimes I think color contributes to it.