My environment: ArcGIS Enterprise 10.8.1 with image server.
We use a hybrid approach based on many of the points you've made. Sometimes we have multiple MDS in single FGDB and sometimes a single MDS in single FGDB and sometimes a single FGDB with a single MDS that is build from other MDS as the input source. Like almost everything we do in GIS data management, the end use case dictates how we decide to package those data and create services from it.
For example, we categorize our orthoimagery collections in four overarching areas: Regional, Municipal, Conservation, Coastal. We have a single FGDB for each overarching category with multiple MDS based on collection year.
For discovery/catalog purposes we have a single FGDB and single MDS including our entire ortho collections. This FGDB MDS has no overviews and is not for visualization, just for discovery of the tile/tiles that cover a spatial or temporal extent. This service is also the input to our tile discovery and download application.
The key to make this work: Attribute your MDS with temporal information and enable time in your services.