Macros don't round down, Syfer22, only up. This is why they are inefficient if you are even remotely serious about your damage output. Also if you spam a macro with multiple GCDs it starts from the top and works its way down adding more time, and it also removes the ability to queue a GCD action (very important in this game).

Unfortunately no one can tell you what's optimal for you, but just what's optimal for them. I personally only use 1-5 and then I have my two side mouse buttons bound to alt and shift (you can use ctrl as well, but it's my push to talk). I also use F, R, G, T. So I can have 1-5, shift+1-5, alt+1-5 and three variations of F, R, G, T. My mouse has a few other buttons that I use for cooldowns as well. In other games I've also used other keys Q, E, V, B. Don't be afraid to unmap and remap things. You just need to test out which of those keys is comfortable for you to hit, but modifier keys are going to give you a fairly large selection. Some people also remap movement keys to ESDF instead of WASD to get more buttons on the left side.