I hit the following error when trying to debug a Visual Web Developer Express 2008 project.
Unable to Start Debugging on the Web Server. The web server could not find the requested resource.
I did not find a create deal of help but UrlScan seemed like a good place to start. After a download, install and uninstall, I noticed UrlFilter in Add/Remove Program. Once UrlFilter was uninstalled the debugging started with no problems.