When hosting ClickOnce applications on Amazon S3 you might notice download problems on some versions of Internet Explorer. Although other browsers does not have problems downloading ClickOnce .application file, Internet Explorer complains with “The requested site is either unavailable or cannot be found.”.
The problem is most probably in the Content-Type of the .application file. It is set to application/binary, but should be application/x-ms-application. To fix it, you have to connect to S3 Management Console and fix the Content-Type under file Properties.