I'm wondering about the same thing too.
Here's what I really want to do:
I'm building a theme where every post can be assigned two or three different lead-images of different sizes. Right now I'm using custom-fields to do this. Like you said, its tedious upload the images and add them to custom fields. A nightmare when you have to do this everytime you post.
To take things futher, I'd like my theme to allow the author of post to choose from images in media library and crop it just like what we're doing now with header images. Here's where I can relate to your question as I wanted the cropped image URL to be automatically assigned to its designated custom fields too. (Or I can choose to bypass the use of custom fields completely but that's a diffent approach)
However, I'm really unfamiliar with WordPress programming. The lack of documentation and tutorials on WordPress api programming is my main gripe.