I'm currently working on an upload tool for a client using .Net to upload via the XML-RPC calls. I am currently hitting two brick walls.
One is creating configurable products. Have I missed some documentation, is this possible?
The other problem is adding data into drop down attributes for things like size. Is this possible via the API?
You can extend the Magento API, here is a blog post as a starting point. As a word of warning, I suspect you will find configurable products to be quite a challenge. If you can manage it, I suspect you will find quite a bit of interest from users wanting to purchase the code... some incentive for you :)