What you’re experiencing isn’t really Cubase/Nuendo’s fault, but will happen on any DAW under unfortunate circumstances. It has something to do with the way tempo changes are processed in some VSTi and effects.
As a solution, try this: on each Kontakt instance in your session (and in VEP if you’re using that), except for the ones with tempo-synced instruments, disable external sync. See the attached pictures:
As far as settings go, on a decent machine, with a big session, with sample rate 44,1/48, I would suggest running an audio buffer size of 128 or 256, ASIO guard on normal (disabled for VEP in the plugin manager) and 32bit mixing engine.