I generally go with the default UI.
Grab something like MoveAnything, to position and/or hide elements.

Then go with as few addons as possible, that give me all the information I want.

Currently, that would be Pitbull Unit Frames - for health, mana, cast bars, target, target's target, and parties target. I use the last, to visually verify all my toons are on the same thing. Some are large enough to read easily (with a lot of information), others are small and just give basic information (such as the name of my target's target).

I really like dot timer, for tracking buffs, durations and cooldowns.

I like BigWigs for warnings, but Deadly Boss Mods for timer bars and the whisper "busy" feature. Basically, use half of one and half of the other, with a lot of stuff disabled in each.

Essentially, I use the basic interface + a bunch of addons I like.
The only custom UI I went with was Mazzle, which was pretty but hardly minimalistic.