Michael,
Absolutely, and thanks for the quick response. Hopefully my detailed process will help.
Different customers provide me with shapefiles (streets, land use, address points, hydrology, zones, etc.) which I then convert into feature classes within feature datasets in a file geodatabase I create on a VM where I have ArcGIS Basic installed. From there, I create four basic map documents: Basemap, Streets, Structures, and Zones. Each map document contains basically the exact same feature classes, just for that particular customer (lakes, streets, houses, various businesses, etc.) From there, I simply save the map document and share as runtime content. I store it all in a single folder.
The folder will contain the four subfolders housing their particular .geodatabase file (so Basemap, Streets, Structures, and Zones). This, along with a created .json file that our app uses to display the runtime content is placed on an customer's server. We create many other applications (not ArcGIS-related) that require users to have full control of the drive and its subfolders in order for those applications to work, and these folders are stored on the same drive. We then create a .bin file that directs to the .json file (which itself points to the individual .geodatabase files).
From there the user, from their local machine, access the server where the application (and associated map data) is stored. When we use this process in-house, we cannot replicate the errors that occur. I will load up mapping application from two different servers, and while the applications are both pointing to the same location where the .geodatabases are stored (on a third server), again, no errors occurred. We have verified that all the permissions are correct for the users.
I hope this helps.