This one took some time to weed out, but found that the Forefront Scan Engine had incorrectly flagged my welcome page in my Site Directory to VirusStatus=1 and was causing an Exception from HRESULT: 0x80041050 error.

Solution:

1. Open your SQL Server Management Studio and go to the Content Database where your default welcome page is returing the error (Usually WSS_Content_[someguid]).
2. Create a new query and run:

   select *
   from AllDocs
   where (VirusStatus > 0) and (VirusStatus is not null)

3. If you get any results this is your issue!  (Given that you don’t actually have some virus in that file.)
4. Run the next query:

   update AllDocs 
   set VirusStatus = null 
   where (VirusStatus > 0) and (VirusStatus is not null)