It's more noticeable when performing oGCD abilities as macros do not queue up if you're locked in frames of animation.

For example as Paladin, if I want to put Intervention on the other tank with a macro, I usually have to mash the button a few times for it to go off, even though the macro has the skill listed, and I'm be in the middle of using another ability, where as hitting Holy Sheltron will queue it up to use at the next available moment, making it always go off. Both of these are off the global cooldown, yet the macro is more cumbersome to use.

There is also the fact that you cannot use the /wait command with fractions of a second, and the GCD is 2.5 so trying to use multiple skills in a row with a macro will always be a DPS loss as you can only have skills set to go off every 3s seconds.