One of my customers have had some trouble with CSS files being cached in the browser for too long after a new version is released, making the site look bad. To resolve that problem I added a query parameter with the current revision to the end of the url, i.e. mystyle.css?rev=123. It worked fine on my computer, but when I sent it to the staging server I got the error "HttpException (0x80004005): '/my/path/mystyle.css?rev=123' is not a valid virtual path.".
After some research it turns out that the home made CSS compressor HttpHandler I'm using calls VirtualPathUtility.GetDirectory to get the directory of the CSS file. On my machine there was a flag set in the registry that allows for the characters ':', '?', '*'. in VirtualPathUtility.GetDirectory(string), on the server it wasn't set.
The flag is called VerificationCompatibility and found in HKEY_LOCAL_MACHINE\SOFTWARE\Microsoft\ASP.NET. If set to 1 it allows all characters but '\0' in the url, if not it will also disallow the three characters mentioned above. Since it has something to do with security my solution wasn't to set the flag on the production machine, but rather to send AbsolutePath to the method rather than PathAndQuery that was used first.
Since it took me a while to figure this out I thought it would be nice of me to let you know, and hopefully save you some time.