I think what I'll end up doing is at least calling gameflow for a couple of series until I get a real idea of what my opponent is calling. If they continue to mix it up, I'll continue to just use gameflow. If they get repetitive, I'll hand pick a play to beat their D.
Things change in context to the score, also. Once I'm up 2 scores in the 4th I'll probably be hand picking plays to run the game out.
Still, I like the idea of starting out with a base gameplan and just focusing on execution and reading the defense. Having my ideal gameplan already put together allows me to focus my mind on other tasks at hand. Usually I do have a few plays picked ahead of time to set up the defense. That takes a lot of attention away from other things, such as the actual current play being run.