Assuming ME = Misery's End, that only applies post 20%. In 2.6 seconds, you get off Heavy Shot, Bloodletter, Heavy Shot. That's 450 potency as opposed to 300. Any way you slice it, with Bloodletter being off your Global and BARELY causing a delay, which I have yet to see where a heavy shot doesn't proc when my GCD completes, it's more beneficial to weave it in between your cooldown every time it is up. Not to mention, it's free TP-wise.
I've never noticed a delay from seeing my other non macroed GCD timers and the macroed ones. They shoot when I click it, and the spam makes bloodletter proc about halfway which allows another Heavy right after.