First of all, if you're new to the game, I suggest reading a general UI guide first (or even instead :). My guide is about hotkeys setup to use keyboard intensively and effectively. It is best suited for characters with lots of spells, abilities and clickies (does it mean ANY character in DDO? :). I play a battle cleric myself, but expect similar setups to be useful for many other classes, casters and monks being obvious examples.
I prefer FPS mode with mouselook almost permanently on. Even in full heal/full caster mode wheh I dont have to melee, I don't like to use mouse to click hot-bars. To be able play this way, I need a lot of hotkeys for my spells. The main idea is not really difficult though:
I could possibly end my guide after this picture. The most beneficial part is the idea to place hot-keys in an easy-to-use-and-remember way. Num pad, arrows and cursor keys give great 26 hot-keyed positions, and only one glance at spell bars should be enough to quickly press just the right button.
Left part of a keyboard around 'WASD' is used intensively too. Q, TAB and ` (backtick or tilda key, just under Escape) are the quickest keys to access in battle along with classical 1-7 for spells and F1-F6 to select group members. I use these keys for heals and offensive casting. (Default TAB behaviour is to cycle through combat targets. I have this functionality on left Shift.)
Some other hot-key decisions:
- Numpad '+': quick access for my feather-falling item.
- Alt + digits to switch weapon sets.
- Not-hotkeyed positions on my bars I click with mouse and/or drag to hotkeyed when expect to use them often.
- Shield block: Middle Mouse Button
- Voicechat: F (default) or Control being another good option which I historicaly do not use.
- Hands-free run: R (default)
- Interaction: E (default)
- First NPC Dialog Option: Alt+E (realy helps to click through long dialogs in a second)
- Cycle through combat targets: Left Shift
- Cycle through non-combat targets: Left Alt
- Toggle mouselook: Ctrl+Space and Alt+Space (or hold RMB to toggle temporarily)
- Character Screen Alt+C [default C is used as a spell bar hotkey]
- Quest XP, kill count, etc: ' [default X used as a spell bar hotkey]
- Examine selected: Ctrl+A [default Z used as a spell bar hotkey]
- Group Panel: G [don't remember the default...]
- Quest Journal: L [don't remember...]
- Adventure Compendium (Favor Panel): P [don't remember...]
I put my ddo.keymap file and some more images into archive, if you need them.
P.S.: I also changed default UI skin and prefer Fade2black. There is a good guide how to do it.
P.P.S.: There's an impressive guide how to setup DDO to use gamepad. Give it a try if you're a console gamer :)