If after creating a click once deployment, you put it on your web server but find that when you run the .application URL, you get a "can't download files" error instead of your application running, check the details. If you're getting 404 errors for the .manifest or .deploy files, chances are IIS isn't configured correctly to support these file types.
By default IIS doesn't know what .manifest or .deploy files are, so it doesn't serve them out. You need to add them as MIME types by going into IIS manager, right clicking on the server name and selecting properties. Click MIME types and add the following;