How much of a performance loss is if I macroed my off global cooldown skills (like assassinate, mug, etc) into my spammable buttons for melee dps jobs?

Sorry if this is a dumb question or something, but I can actually run okay with it, because those skills will fire whenever they are ready, reducing the number of short cooldowns I have to keep my eye on.

Then, I'm asking this because I'd love to know how better you'll get if you weave them between your combo sequences manually.