SD (and other res based sets) how do you?

(DEFENSE based of cours, sorry)

How do you deal with crazy accuracy buffs (Nemesis vengeance, DE's crystals)?

You can do two things: Not fight them, or pop purples until your defense is high enough.

The hit-code is unfair for defense sets. Resistance debuffs increase damage done to a target by the percentage of the debuff, so resistance sets don't have to worry about taking much more damage than they already are taking. Defense debuffs had the potential to make you take more than double the damage on the first application and then start taking 3, 4, and 5 times more damage than you originally took. Defense debuff resistance helped reduce that issue, but getting close to 100% DDR is only possible with certain builds. To-hit buffs on the enemy end up being a direct counter to defense. Instead of multiplying their hit chance by the percentage, it effectively lowers your defense by the value of their buff. A change to that system is needed in order to make the game fair for both resistance and defensive sets.

I avoid DE. They're pretty easy to avoid at 50. When I can't avoid them, I Shield Charge into the mob instead of gathering them up for Soul Drain first. The knockdown keeps them from spawning the quartzes right away, so I can kill the quartz spawners before they do so. If they drop one, I generally drop dead, since I play at high difficulty so they kill me in seconds. My /SR Scrapper, with no Shield Charge, just avoids DE.

Nemesis are easy, I pull the spawn around a corner (so they won't Vengeance the next spawn) and kill the Lieutenants last.

Rularuu, I kill the eyeballs first, and fast. Once those are down, they're just like any other enemy group. If it's an eyeball-heavy spawn, I eat some oranges first.

Orange inspirations, for one, as a general rule. But I take Tough as well.

Never really had a problem with Nemesis. Just have to kill the lieutenants last. That's more tactical than an out-the-gate issue. Same for Quartz emanators from DE. After those buffs are up, though, I can't really tell you other than "pray you take them out before they get you." Dealing with those groups requires a mindset that says "an ounce of prevention is worth a pound of cure."

I have not dealt with Rularuu for a good long while. Can't really say. The others' advice seems sound in that regard.

DE crystals - Kill it fast before they kill you. If it was enough of a problem, I'd make a targeting macro as Doomguide suggests.
Nemesis vengeance- Kill everything but the lieutenants first, bring the lieutenants down, and AoE them to death.
Eyeballs - Avoid the Shadow Shard. I mean really. But if you MUST go there, avoid eyeballs. Wait, you're in the Shadow Shard fighting eyeballs? What's WRONG with you??? *sigh* Kill them fast I guess?
Arachnos - Kill tarantula mistresses fast. If necessary, create a targeting macro.

When all else fails, skittles. Taste the rainbow. Or "You do what we do, run. You run your *** off."

"every situation requires your patented approach of shoot first, shoot later, shoot some more and then when everybody's dead try to ask a question or two." - President Grant, Wild Wild West, or thereabouts.

Kill 'em all, kill 'em fast. Accuracy only counts if you give 'em the chance to shoot at ya.

I was hoping a "You just have to you this -grossly-expensive-IO-that-does-the-work-for-you-" answer. But thanks for the replies, I will try to play smarter.

About Nemesis leuts, if the leuts cast vengeance so I should kill them 1st and not last? Or its some kind of special vengeance that triggers on death?

The DE Quartz pet is the one true kryptonite for a defense based character; always, ALWAYS look at a mob of DE before jumping in and if you see a big pink crystal dude target him FIRST and kill him NOW. By the way, the DE pet summon is NOT interruptable... either knock him on his butt before he aggros or be prepared to IMMEDIATELY kill the Quartz pet as it summons.

As I recall that Quartz pet gives all DE in the rather large AOE a massive (on the order of +100%) tohit buff... effectively every DE in the area will have a 95% chance to hit you through soft capped defenses. You'd need on the order of 145% defense to soft cap yourself against buffed DE. Since this isn't practical you have two choices, kill it before the DE kill you or kill the Guardian before he drops it.

Shield Charging spawn at start doesnt help. Just tryed, they just summon Quartz later, and unless I pop a couple of orange I'm toast in the next second the quartz hit the ground.