If you can prevent any software from sending a clock via the USB interface, I think you should not experience issues. Things would be even worse if you send it different clocks via MIDI and MIDI-over-USB. Imagine it gets a clock via both that will probably not work too well, since they won't arrive at exactly the same time. The NS2 will try to sync its internal master clock to any MIDI clock it receives, be it via MIDI or via MIDI-over-USB.
In contrast to my statement above, and answering your last question: yes, there may be issues if you leave it enabled and also connect it from some external interface. In the MIDI menu, you can choose MIDI channel 1.16 as well as MIDI-over-USB channel 1.16 as in- and outputs.
If you connect the NS2 via a separate MIDI interface (which is what I did, because the timing seemed 'tighter') you can just ignore the MIDI-over-USB functionality of the NS2. You don't need to go through all this trouble.
