It really depends on the kinds of applications you want to develop. For most purposes these days, C# and .NET are completely suitable. However, there are certain kinds of applications that need as few dependencies as possible (shell extensions come to mind) that are not practical to do as .NET applications. For those you would need Win32.
As always, it pays to have at least a basic understanding of Win32 even if you’re using .NET for most of your work.