Cool project @bsmtdweller
New thread or stay in this doesn't matter much, but for people searching the forum (or their favorite search engine) in the future, I think a new thread with a subject containing "incubator" will be more clear.
I would build it with multiple nodes. Smaller chunks of code, easier wiring, easier to isolate individual parts which helps tremendously when troubleshooting, easer to reuse code for one node in case you (or someone else) want to expand the project later, easier to remove a part if you (or someone else) don't need it.
The non-mysensors code is more important, so I would start with that, but make sure all parameters that you want to be able to change are stored in variables and not hardcoded. Then add the MySensors code to update the values of the variables.
The autonomy will be hard. Normally I would prefer to have all logic in the controller, since a controller has much better ways to program and debug stuff. Not fun to write - and maintain - in C with very rudamentary debugging tools. But as you say, being reliant on having Domoticz working all the time might not be good. Having the system fail gracefully will be a challenge. A start could be to search the forum for MY_TRANSPORT_WAIT_READY_MS to see what others have done. And maybe - to make the system as reliable as possible - you should add everything to a single node instead of splitting it up into multiple nodes.
Understand it might be annoying.. We run the latest version of the notif-plugin mentioned above (0.3.1). So it seems they still have some issues. They had an issue (which is closed) that sound like the things you experience.
I can't seem to find any related user setting in my account either.
sorvani created this issue in psychobunny/nodebb-plugin-desktop-notifications
Desktop notification banner never goes away