I am having a hard time right now dealing with a huge VS.Net 2008 Website.
We are using a CMS Solution which contains many features for the site. Navigation through source files in the VS.Net IDE seems to be slower and slower. This is due the fact the compiler continues to recompile the modified files as you make changes. I prefer to work with Web Application projects because I am more in control with the compilation and I actually we a compiled dll instead of hundreds for assemblies for vs.net websites.
One of the solutions to fix this problem is to remove the CMS features that I am not using so that the website can compile faster. However, this is not an option based on client feedback.
My recommendation is that if you intend to have a large site, use Visual Studio .Net Web Application Projects instead of Websites. Trust me!