It's more about IIS and your DB server's performance than DNN. Go straight to the source and visit the relevant tech centers on this site: http://technet.microsoft.com

The main tip I have is to devise solid procedures for everything you do. Backups, restores, upgrades... all management tasks, including those outside the server such as managing clients, domains and payments. Keep a rolling diary of everything you do and never get too comfy. Do not entrust your host with all of your backups - make your own and transfer them somewhere.

Also, more DNN-specific: Have plenty of hardware resources so that you can negate those when troubleshooting, regularly restart application pools, occasionally restart the server - and clear out the asp temp files for a fresh build after a restart. Always recycle the pool and occasionally check and/or reapply permissions before applying upgrades. Examine the various logs every day and figure out what causes every new warning or exception. Keep records all the way. I've been upgrading and maintaining the same instance for three years and it's still as good as new.

Rob

edit: And visit the DNN forum and related blogs at least a couple of times a week.