I come from a Pro Tools background, but have halfheartedly switched to Nuendo.
One aspect that is cumbersome for my workflow is having two channels for one specific virtual-instrument. I can see why it is beneficial to keep them separate, however, have an option to have a combined channel as it were in Pro Tools which was quite easy to work with.
What makes the workflow difficult when using VIs is I have one channel for the audio output, and another channel for the MIDI input and my surface console gets cluttered or just full. If I have too many VIs and run out of faders, I have to page back and forth which slows down my operation.