This is the way.

I use

Main keys:

• Primary DPS (usually a builder), Opener DPS
• Secondary DPS 1-2
• Tertiary DPS 1-3 (usually primary resource spender or cooldown)
• Interrupts 1-3
• Defensives 1-3
• Stealth/Escape spells 1-3
• Taunts or additional CC 1-3
• Heals, dispels, etc. 1-3
• Movement spells (sprints, etc.) 1-3

Additional keys:

• Coooommmbbboooooo Breeeaakker (macro’d trinkets or covenant abilities, etc. just slam that baby when I need big dick energy)
• Mounts (land, flying, vendor, etc.)

They decrease in importance with the modifier key. So for example, my defensive keg will have X as my primary defensive (iron fur), X+Ctrl as my short cooldown defensive (bark skin) and X+Alt as my long cooldown defensive.

I use a keypad, which is particularly useful with this approach because it has a directional pad and space bar that can be operated with a thumb, leaving four fingers for abilities at all times.

Then I put targeting stuff on mouse wheel (same principal, mouse wheel for next/prev enemy, Ctrl + wheel for next/prev friend, etc.) and jump and autorun mouse 4 and 5.

Oh and I also have some misc oPie rings (hearthstones, professions, etc.) bound to like Alt and Ctrl with mouse or out of the way keys.