Since the release of the expansion, I've tried to keep my interface clear and simple. I've cut back on mods and what not since I needed a huge amount of add-on memory consumption for Quest Helper (the thing takes up more than my entire UI).
However, since my rogue was fully geared and my death knight hit 80, I realized that since mobs weren't dying before I could even use all my runes, I needed a better way to monitor them than the default UI.
After some trial and error I've come up with this:
Click me.
I tried using MSBT at first, but I didn't like the way it scrolled, and I was rather fond of the game damage. I may decide to go back to it later, but for now I'll stick with default+the original SCT.
Pitbull for the unit frames, and Magic Runes for the rune detection (colored bars above my player frame). Between the target frame and the bars is where the target of target frame appears.
The UI is set up to provide me with all the information I need in places that are very easy to glance at without having to move my eyes to far. I'll watch my character to check my spacing and watch for AOEs, and glancing to the left I can keep an eye on my rune timers, runic power, and relevant DPS cooldowns. Checking where I'm standing I can see if I'm standing in anything dangerous and also see my swing timer, global cooldown bar, and disease timers.
The rest of the UI is designed to be aesthetically pleasing, but as I'm no good with eePanels or other similar mods, and I refuse to download compilations, this is the bet I can do.
The bar near my player frame has any cooldowns I may use in pvp or pve, but none of those are bound. All of my abilities are bound and hidden. On the bottom I have things I may click like my vent-macro button, army of the dead, vanity pets, mounts, and professions. I think I may set them to fade out during combat, but who knows.
Oh and then I use Power Auras for lots of things: gargoyle, icebound fortitude, lichborne, unbreakable armor, unholy blight, killing machine, freezing fog, and my stances.
The green artsy-looking circle on the bottom changes colors depending on what my stance is.