Michael,
Unfortunately, our application only uses ArcGIS Engine (just loading individual layers into the MapControl, not saving or interacting with any MXD files), so we don't have any experience with ArcMap or MXD files. As a result, I don't have any other thoughts to pass along.
As noted in the forum entry I referenced in my earlier posting, it does seem that Esri has made some changes to the way database connections function in ArcGIS 10.1 (at least, for Query Layers).
Perhaps there is also some difference for the work flow being used in your application.
Sorry I could not provide any better information.
Scott