Good you brought this up, since this is a very important point for a well designed hotkey system.
if my hand's on the mouse most of the time in the game, I'd rather not reach too far across the keyboard (1 to Backspace, F1-F12) or check that I'm getting the right keys to get things done.
StarCraft 2 (and to an extent, 1) made sure to keep all hotkeys to the left side of the keyboard. The main keys you'd be using are CTRL, SHIFT and 1-6, so anything else you may have to access placed in their vicinity.
Windows 8 has its hotkeys concentrated around the Win (flag) keys (both right and left on most keyboards), since this is used to trigger most new hotkeys (so many good ones).
The standard way of placing your hand on the keyboard for IE games, I believe, is your thumb on the space bar (pause), your pointing finger on Q (quick save), and your index finger on TAB (highlight interactive items). Z is used for resting, and the number keys + ctrl/shift for selecting characters, and F# keys for abilities. It covers pretty much 99% of usage scenarios while in the game window, all neatly placed on the left side of the keyboard.