Dave,
Your map in AGOL is not directly tied to your .mxd in ArcMap, since that is stored locally on your machine. If I'm ever in that situation and I need to add a new layer, I just publish a new hosted feature layer from ArcMap into AGOL and add that to the web map. Then you will only have to configure that one new layer, and all your previous additions to the map remain the same.
The only downside to this workflow I suppose is that then not all of your layers in the map are stored in the same hosted feature layer. But that's never been a huge problem for me, since it doesn't really affect the user of the web map. All the layers are there in the table of contents, which is usually all that matters to the user of the map.
Hope I understood correctly and explained adequately!
Cheers,
Katherine
Best,
Katie
“The goal is not simply to ‘work hard, play hard.’ The goal is to make our work and our play indistinguishable.”
- Simon Sinek