How many instruments are you looking at?
Right now , I'm working with 512 samples latency and 1* internal buffer multiplier with 32 instruments on a machine considerably less powerful than yours (... with Nuendo 5.1 on the same computer). The CPU meter is constantly below 50%, most of the time around 20%. I get clicks when I move an instrument while it's playing, but that's part of the game.
... I don't really understand what you mean by "Nuendo's latency compensation". Are you using the hardware inserts of Nuendo?
/Dietz - Vienna Symphonic Library