Using a Xanthia theme and all the right settings can do wonders for the load speed of your PostNuke site but the basis of a fast site is always a fast server. So if you have any influence on the configuration of your server, make sure that it is the best available.
Upgrade To The Latest Version of PostNuke
It is always recommended that you keep up-to-date with the latest version of PostNuke. The code is constantly being reviewed and updated to allow for the most efficient performance. Probably the most important reason to stay on top of updates is for the sake of security.
Use Caching in pnRender and Xanthia
Enable caching in the pnRender module to see performance increases in many modules. Of course, only "pnRenderized" (or "templated") modules will benefit from this setting. But as more and more modules are templated, more and more performance increases will be realized.
If you are using a Xanthia theme (highly recommended) be sure to enable caching in the Xanthia module. Then be sure to generate a configuration cache to help it along.
Statistics Module Hogs Resources
If you don't need the Statistics or Referrers modules, you can deactivate them for added performance. Both of these modules add multiple queries each time your site is accessed, which slows it down. As an alternative, you could sign-up for a Google Analytics account (whether this is a performance benefit is yet to be determined).
Block Reduction
You can increase page loading speed by reducing the number of blocks you display on your site. If you have any blocks that are not being used (deactivated) and you have no plans to use them in the future, you should remove them as well. Even though they aren't displayed, PostNuke has to determine whether to show them or not, which adds more queries to the equation.
MySQL Cleanup
Make a point of visiting your MySQL database from time to time to optimize it. Much like defragging your Windows hard drive, MySQL optimization will allow your server to access your site's data faster. DB-tools normally have an option "optimize" that you can apply to all tables.
Third-Party Modules
Some third-party modules allow you to run optimization utilities to keep things running smoothly. PNphpBB2 (forum) is a great example of this.