The solution was to remove the website in the CF 10 Web Server Configuration tool and add it back! Also, I used the web.config from http://wiki.coldbox.org/wiki/URLMappings.cfm as that was required to complete the setup.
Hope that helps!
Yeah I am guessing that the website didn’t have the ISAPI filters installed, the updates clearly stated that these must be removed and re-added at times. Although I must admit I have never had an issue expect at one particular update.