In the case of off-gcd macros, the only problem I've see that actually matters is when it sorta glitches out. I've run into several instances where it either cancels itself because of animation clipping (where the off-gcd ability does half of the animation then cancels itself, forcing you wait on the gcd to recycle, making you lose 0.5-1sec of dps) or it goes on cooldown despite not actually being used (or at least not being document on the log).