Came in this morning and was smacked in the face with this... 

I'd been dorking around in the project in somewhat strange places so this wasn't a complete and total surprise.  I reset IIS, restarted the comp, went into the web.config and searched for red squigglies, rebuilt the solutions a billion times, cleaned the solution, looked at the error output, no help.  After a random web search and seeing suggestions that I've already tried, I go into the asp.net config settings within IIS for the particular app I'm working on (maybe I set it to v1.1? nope), click on the tabs and I get this surprisingly useful error.

...Debug cannot be parsed ..."On is not a valid value for boolean".  This also gives you a line number...gasp!  I jump into the web.config and sure enough on line 9 ....

custom error mode on, debug mode on ...how quaint ...thanks vstudio for not pitching a (useful) fit!  If you ever run across a strange cannot debug error, I suggest going into the asp.net config and clicking on the tabs!