I run Ultra, with post-processing off, and the Hardcore version of DarkD3. I really don't like the oversaturated colours of GW2, I feel they're artificially boosted, perhaps a last-second course-correction to try and ape the "toon" look that's so popular thanks to WoW. DarkD3 pre-sharpens, so textuers regain some of their detail from being filtered out by the engine, and it colour-corrects the whole scene towards liver (blueish), which isn't to everyone's taste, but I prefer it that way. If I turn it off while playing now, the whole world becomes superflat and ultrabright, eye-seeringly primary colour assault. I'm acclimated to my settings, as many are acclimated to the "natural" way it looks.
I run SLI x GTX 560 SEs, 8GB RAM (which I really need to raise), and an i5 clocked from 3.8 to 4.2.
But mostly, turn off post-processing in-game. It washes everything out with too much bloom, and makes fights almost unreadable.