What i mean is - if you have any nodes that perhaps output to MQTT or to Database that you DONT want the 2nd instance to perform (as it could muck up the data first instance) you should change them or disable them so you dont have issues when you finally allow the 2nd instance to RUN.
Once both are running, the first instance may wellstill be doing all the work (initially) but you can begin to transfer logic between the two, you disable 1 part (in NR1) and enable (in NR2) that piece of logic (as quick as possible ;)). there are ways of minimising outage though (only you know your logic)
There is no real science to it - all i can really say is your approach (to minimise downtime) should be logical and staged.
To clarify, safe mode doesnt start your flow (node-red starts but flow doesnt execute) - so you are SAFE to run both instances. My point was when you DEPLOY changes to the 2nd instance - it WILL start running the flows (i.e. it drops out of safe mode)