The larget site we have build has about 6,000 pages, it's an intranet for the Moving Picture Company (MPC) managed by 500 odd employees and SilverStripe holds up just fine. That is as long as you can handle having that size of site tree, which obviously can get quite unwieldy. That site also has *thousands* of files, although we are using the TinyMCE image file/manager instead of the build in SS aset manager as the primary file uploader/manager. However if you are using a modern browser in your org then you might also look at Kick Assets which has some awsome HTML5 file features: http://www.leftandmain.com/silverstripe-screencasts/2011/08/25/introducing-kickassets-give-assetadmin-the-boot/
Also for a large tree this snippet is indispensable: http://www.ssbits.com/snippets/2011/making-the-tree-tools-sticky/
I also guess it depends on the type of content you want on the pages, if you have hundreds/thousands of 'pages' all under the same parent then you would be better off using the techniques mentioned by swaiba to make DataObjects behave like pages managed via ModelAdmin. We are very close to releasing a module that should make this process super easy :)
In terms of the Multisite module, it is a pretty good starting point for multi-site management, giving you a nice site switcher and tree per site, but it is limited in terms of sharing content between sites, as Swaiba mentioned we had to do some pretty extensive development to male it work for our client.
Anyway if you have any more questions just let me know :)