You have to decide how confident your team is with client side frameworks. Development of Single page applications may not be easy in the beginning, but you will get used to it very quickly. It's very important to give your team the right training.
In my opinion, Durandal is the simpliest, most elegant and complete framework to build enterprise level SPAs. It is important to know how knockout, requre and durandal's router and composition work. For data centric application I would use breezejs to manipulate and cache data on the client side and request it from the server side. Breeze works best with Entity Framework on the server side, but it's not necessary. If you can use Entity Framework, it will simplify your development, because it can generate metadata of your database structure for breeze. If Entity Framework is not an option, metadata can be written by hand.
I would make server side as thin as possible. Serving data from your database using web api with ORM of your choice and some cshtml pages.
Durandal Get Started is a good place to start.
Durandal Auth is a very good template for enterprise level SPA. It may not suit you completely, but you can use it as a guidance to build different modules of your application.
Breeze samples I suggest you consider using breeze. There are good courses available on pluralsight.
Knockoutjs has good training on data-binding.