It has been proven by numerous sites that EPiServer CMS can handle huge amounts of content. Doing so does bring a few challenges though. Here's a few few patterns that I've identified when it comes to building large scale EPiServer sites with great performance.
Lately I've been working on a little module for EPiServer CMS for listing and creating contents in other ways than using the page tree. I call it PowerSlice and it's now available for download.