the problem seems to be initial load time, due to jit compilation. If you have direct access to IIS mdoify app pool settings not to unload after 20 mins of idle time, otherwise use a keep alive service, to avoid time out of the site.

To improve speed of subsequent page calls, modify the performance settings in host settings (use heavy caching, deflate compression but not whitespace filter).

Frequently clean DotNetNuke eventlog, scheduler history and site log as well as database transaction log.

http://www.snapsis.com/PageBlaster.aspx

This module really improved my page load times. I was fed up with slow response times developing the site never mind browsing it!