Hi Jay Mathis,
In case you use RadUpload "Prometheus" where the RadUploadProgressHandler has an ashx extension instead of aspx you should not add the RewriterRule in the SiteUrls.config file which is necessary in case you use the classic RadUpload.
I mean that if you use the classic RadUpload and you have a DNN URL rewriter (referred to as "friendly URLs"), you will need to exclude the RadUploadHttpModule. Otherwise DotNetNuke will intercept the request and you will see the portal default page instead of a progress area. Open the SiteUrls.config file from the DotNetNuke\Website folder in a text editor and add the following before the other <RewriterRule> tags:
As far as it is concerned to RadUpload not always being skinned properly if the DNN is running on an IIS subapplication I suggest you check whether all WebResources are loaded correctly and whether something may prevent their proper functioning.
Do not hesitate to contact us again if you need further assistance.
the Telerik team