When I first saw the 12 buttons on the side of the mouse, I worried that it would be impossible to keep them all straight; how would I be able to tell which button was which without looking... and how clumsy would I be with that many buttons all under my thumb? As it turns out, the design works pretty well. Twelve of the editable thumb buttons are in a three by four array, but the tops of these buttons are grouped into two concave groupings, making it easy to tell the top six buttons from the bottom six and, from the feel of the button, whether it's the top or bottom of the oval and whether it's left, right or center.
Personally, I found that I arranged my actions differently to make better use of the array of buttons. When I used the action buttons on the keyboard, I would arrange my actions starting with openers, then builders, then finishing moves, with health and buffs on the far right side, so I could keep most of my button-mashing on the left side of the keyboard. However, when using the G600, I could group openers on the top left corner of the button array, with builders cutting a diagonal from top right to bottom left and finishers down towards the bottom right corner. In this manner, I didn't have to worry about accuracy of my button presses as much. I could sort of "squish" the side of the mouse in and roll my thumb around a bit to hit similar actions, working my way from the openers corner down to the finishers corner. This worked pretty well for me, while keeping my right hand on the mouse a lot more, rather than having to switch back and forth between mouse and keyboard.
With the free downloadable customization software, you can assign each of the buttons on the mouse to be either a keystroke or a mouse action. Note, however, that while these are customizable keys, they don't do multi-key macros. I can think of a few things I could have done if it had the ability to do multi-key macros, but its quite functional without that.
There are three customizable profiles in the G600, and the keys and color customization options can be set differently for each of these profiles. If your gaming rig has a special lighting color scheme already, you can use the customization software to tailor your mouse's 12-button array to suit. By selecting how much red, green or blue to add into the mix, you can match the colors on your keyboard, audio mixer or other existing hardware, if you like. In addition to selecting the color, there is an optional fade effect that can fade the lights on and off at an adjustable speed. There is also a color-cycle setting that will rotate through different colors.
If you play an MMO character with a controllable pet or assistant character, the default profile might be just right for you. This puts the top row of keys (numbers with "-" and "=") on the 12-button array and Control plus those keys in the alt set accessible by holding the Shift button, the button to the right of the right mouse button, which rests under the ring finger. In this way, you can easily keep your right hand on the mouse, while sending commands for your character and your character's assistant. Pretty sweet.