If you are planning to release the applications as Free software, many will want a unix-ready version of the program... meaning Tk is more appropriate.

If the program relies on Windows for something else, or your target audience is a large group of Windows users, then go with Win32. Isn't that an automatic part of the ActiveState distro (if so, that is one less step and break point during install).

I don't find the interface to Tk to be unfamiliar on Win32, in fact, it cooperates with Windows better than some other applications I've used on Windows.

Have you used the Windows API in any other languages? If so, that might be more comfortable than learning the ins and outs of Tk.