Update: Scott Guthrie help me to get in contact with Steve Molloy and Matt Gibbs at Microsoft about the original issue in this post (Read more about The WebResource.axd handler must be registered in the configuration to process this request - not related to Vista or Cold Fusion).
Steve has been running this in the stress lab for a couple days. After several hundered machine-hours of stress while touching config every 3 minutes they have not been able to reproduce the issue.
This is probably a race condition that occurs because the framwork or application we have does something special. But I have not been able to create a simple reproducable test case. Has anyone?
I have identified several things that increases the probability to get this issue:
* You have login controls or other controls that uses validation on your start page. (Validation needs javascript and EnsureHandlerExistenceChecked will called because Webresource.axd is used)
* You have a lot of assembles in your bin folder.
In my case, the framwork I use (EPiServer), has code that loads all assemblies in the bin folder in the constructor of the global.asax class. It does this because it looks for classes with plug-in attibute. This in combination with the call to EnsureHandlerExistenceChecked on the start page does probably increase the risk for the problem.
/Fredrik
Read more comments about "The WebResource.axd handler must be registered in the configuration to process this request" in my blog.