And don't run the game clock, either. If the ball is ready for play, get the fuck out of the way, ref, and let the game play. If it's not ready then stop all the clocks.
And if you're going to allow the defense to "respond" then why don't you let the offense respond to the defense's response? The only real problem for you, ref, is making sure that anyone who comes in, stays in for at least one play. That isn't too much for you, is it? But then, we'd have to let the D rerespond, and so on. Actors, reactors, rereactors, rereactors rereacting to the preactors.
Maybe limit substitutions? If the O sends out three new guys, let the D send out up to three. Wait, though, the D shouldn't have an advantage, so if the D "over-substitutes" by sending in more players, then the O should be allowed to add players, that would be only fair, right?
Or signal "ready". Yeah, there we go: let the HC on each sideline wave a flag, or maybe a large, colorful foam hand, when his (or her) team has reached a point of readiness, and then start the clocks. When one guy signals, the other guy has five seconds to respond and play may start.
In fairness to all involved, the HC shall designate a designated Signal Flag Handler, from a group including the HC him (or her) self, the official team Mascot, Band Major, or any sufficiently rude Yell Cheer Leader.