I've seen this issue in several different permutations, but every fix I have found does not apply to my situation AFAIK. I have a few VS2013 (.Net 4.5) MVC/WebForms projects. I just upgraded (well, HelpDesk did) to 2015 this morning, after which as soon as I click Start Debugging, I get an empty IE window and an error "Unable to start app...Access Denied." I can start without debugging and then attach the debugger. I can also start the same projects in VS2013 and launch/debug OK. If I create a barebones MVC app from scratch, I get Access Denied. The Documents\IISExpress logs show no error, and I've tried wiping out all old web site configs from the IIS config file. I've rebooted the computer, I've checked out to a brand new project workspace.
NOTE: I cannot run as an admin because my domain prohibits it, so that is not an option. I am still in the Debuggers group (again, I can debug completely in 2013, and I can attach in 2015). What is broken in 2015 is StartDebugging.