According to "SDY" here:
http://social.msdn.microsoft.com/Forums/en/vsdebug/thread/ff3cda97-8772-4a62-a54b-e4faf5b8cffaYou simply:
In Project properties -> Security I unchecked the "Enable ClickOnce Security Settings" and then it worked again.
Further down, "SteveC_Sharp" offers this as well:
GOTO the Project security tab and do this
1. Click 'This is a partial trust application'
2. Click Advanced Button (toward the bottom)
3. unClick 'Debug this application with the selected permission set'
4. Click 'OK'
5. Click 'This is a full trust application' (this will undo step #1)