Wow, this is a 'long question'. You might want to consider building it in a way you are most comfortable with e.g. data in DB, layout in aspx, dynamic/static WebControls etc.
Get it working before polishing, then run series of tests to have a idea of the performance and scalability. Caching mechanism can be a useful start.
This is by no mean a complete answer, just something to start the ball rolling.
If performance is top priority, nothing beats static html.
So, what do you think of making a system so the Administrator can change the layout and then save the generated page as html, so the webserver can pick it?
From CodingHorror.com
What's Movable Type's performance secret? For the longest time -- almost 5 years -- I used the version I started with, 2.66. That version of Movable Type writes each new blog entry out to disk as a single, static HTML file. In fact, every blog entry you see here is a physical HTML file, served up by IIS just like it would serve up any other HTML file sitting in a folder. It's lightning fast, and serving up hundreds of thousands of pageviews is no sweat. The one dynamic feature of the page, comments, are handled via a postback CGI which writes the page back to disk as each new comment is added. (This is also the source of the occasional comment disk write collision, when two commenters happen to leave a comment at the same time.) Yes, it's a little primitive, but it's also very much in the spirit of KISS: why not do the simplest possible thing that could work?