Diablo 3 Ergonimic Keybindings Guide submitted by tn.

PROBLEMS

The default Diablo 3 keybindings assume that all your fingers are of the same length, and with prolonged use this can stress your hand.
Keys reachable by the pinky finger can cause your entire hand to shift. (except the ESC key). Thumb can't reach ALT key easily.
Frequently-used Panels have keybindings that are so far from your skill keys, and can be easy to forget. Example, Chat is "O" and Achivements is "Y".
You cannot use "A" key, because once you use it, the Auction House on the Main Menu cannot be triggered with "A" anymore.
The most important Kiting command, "Move" is unassigned by default. This is needed to make kiting a breeze. (More on this below)

A HAND-HEALTHY, ERGONOMIC SOLUTION

The Mouse

First let's take advantage of your mouse wheel, with the most important commands:

Binding	Command
MWheel Up	Inventory
MWheel Down	Show Item Labels (Alt)
MWheel Click	Potion

As with all keybindings, it will require you to practice and adjust until you get used to it -- and it's gonna be worth it!

Natural Keyboard Bindings

I want to show you how King Leoric plays Diablo 3:

Ergonomic Hand Position as demonstrated by King Leoric:

Have you tried imitating that position now? Isn't it comfortable to play like that for hours? Of course!

It is designed, such that Action 4 is the most frequently-used, and Action 1 is the least. Forefinger rests in R. Middle finger on 3. Ring finger on 2, and can reach 1, too.
We move the "Reply To Last Whispherer" command from R to E.
Hold-Attack is moved from Shift to Tab. Pinky finger is now happy.
Toggle Map is moved from Tab to D, easily reachable by the forefinger.
Your thumb rests on the spacebar, the Move command.

Finger	Binding	Command
Thumb	Space	Move
Forefinger	R	Action 4
Middle Finger	3	Action 3
Ring Finger	2	Action 2
Ring Finger bended left	1	Action 1
Pinky	Tab	Hold-Attack for Ranged

"Move" key is very important for Ranged Kiting.

Two cool ranged tips you might not know!

If you are attacking a target with a projectile attack and hold down your mouse button your character will auto aim wherever they go. No need to even move the mouse. Just remember to start clicking to switch between targets.

If you have a secondary move command like mine is spacebar you can hold shift which normally keeps you in one spot when you attack but if you click, hold shift and hold space your character will move after every attack until another attack is ready. This is nice for fleeing targets and to keep you away from incoming projectiles!

Forefinger also has easy access to:

Finger	Binding	Command
Forefinger bended left	E	Reply to Last Whispherer
Forefinger bended right	T	Town Portal
Forefinger curled left	D	Toggle Map
Forefinger curled right	F (unchanged)	Follower Panel
Forefinger stretched right	5 (five)	Skills Panel

You can extend this to other panels, too:

Finger	Binding	Command
Middle Finger curled left	W	Achievements
Ring Finger curled left	Q	Quests and Journals Panel
Pinky Finger stretched	`	Toggle Friends Panel

A Workaround to Lock Your Skill Bar

Make sure Elective Mode is on.

Step 1: Select the skills you want.

Step 2: Turn Elective Mode off.

Your skill bar is now locked.

Get used to this config and your hand will be very comfortable!

My numbing fingers problem is gone.
Painful wrists gone.
Bunched fingers pain gone.