It sounds like you want to build a Rich Internet Application (RIA), not a website, so I would suggest a technology that was built specifically for RIAs such as Silverlight or Adobe.
This might be a biased opinion since it's the only RIA technology I've worked with, but I'd suggest Silverlight for you. I find it extremely easy to work with, and it's built on the .Net framework so you can use C# for the back end (which you said you were already familiar with before I edited your question)
A possible alternative might be HTML5, although that is not officially released yet and is not fully supported in all browsers. I have personally not worked with it either, so I cannot say for sure if it is capable enough to build browser-games with.
As for ASP.Net MVC, that language is more for building websites, so I wouldn't recommend it. I can't imaging trying to build a tower-defense game in ASP.Net MVC....