[Lucid:]

I recently bought a mouse with two side buttons, so I mapped some items to that. I set my sightstone/wards on 3, trinket on 4, and then put my items in order of importance:
Big Mouse Button (6) > 2 > 1 > Small Mouse Button (5) (it's harder to reach with my thumb) > 7

With multiple actives, usually my mouse is for items I use ALL THE TIME like Talisman. I always gotta go fast, and sometimes in really long drawn out fights I can even use it twice. 2 is usually for items that save me/others, like locket, mikaels, or zhonya. 1 is for the less-important or less-precise of that list if I have multiple (example: Mikaels goes on 2, locket goes on 1) or for items like randuins. Small mouse button is great for items that I don't have to use in teamfights, like banner of command, or spooky ghosts! I have to reach my thumb forward to click that button. 7 pretty much only gets used for pink wards when I have no other spots for them.

I think I just got so used to pressing extra buttons that the HUD change didn't affect me that badly. I don't usually check to see if the item is actually off cooldown or not, I just press it! xD Usually the item is available, unless it's Mikaels. That one always seems to be down when I need it most. xD