For most needs on the desktop you wont need to know the Win32, however there is a LOT of Win32 not in .NET, but it is in the outlaying stuff that may end up being less than 1% of your application.
USB support, HID support, Windows Media Foundation just off the top of my head. There are many cool Vista API's only available from Win32.
You will do yourself a large favor by learning how to do interop with a Win32 API, if you do desktop programing, because when you do need to call Win32, and you will, you won't spend weeks scratching your head.
