I'd like to develop an app that runs natively (self-contained executable) for both Mac and Windows that will detect/poll for a USB device being inserted and send an HTTP call as a result. I'm mainly a Ruby programmer, so ideally I could do this with a combination of Macruby/IronRuby and shared libraries, but it's looking like libusb requires a special driver to be installed on Windows (which I can't expect the clients to do). 
Are there libraries/gems that would facilitate this? Is it possible to do what I'm describing using Python/Ruby? It's not as important to be shared code as it is that the codebase is Python/Ruby/single language. libusb would be ideal if it didn't require an install of a special driver on Windows.
Well it is definitely  possible; I don't know what the equivalent is in rubygems by pyUSB is a easy to use module you can leverage to do this and then there are numerous http libraries for python.
As for making it self contained, it is possible but not ideal. py2exe is a program that basically takes a copy of the python interpreter, all dependencies used in your programs and your script and glues it all together in a exe file, but by default py2exe will not pack it into a exe, but there are instructions on the wiki
Cross-platform USB development for Mac/Windows - possible with Ruby/Python?