I had previously installed the VS11 beta, and had some issues with my Visual Studio 2010 instance, which you can see here how they were resolved: Excel AddIn Click Once depl
I've found the issue which was not letting me run my project in 'Debug' configuration mode, though it worked in 'Release' mode. At some point, the AddIn, got hard-disabled (not sure if that's the term to use). At that point, trying to re-enable from within Excel doesn't do anything. Within the registry, there is a folder where disabled AddIns are flagged. I deleted all of the keys from this folder except for "(Default)" and now my AddIn works when launching from Visual Studio 2010 in 'Debug' mode.
HKEY_CURRENT_USER\Software\Microsoft\Office\14.0\Excel\Resiliency\DisabledItems