Thanks to Dropbox my photo sharing site has the world's best uploader. (1) Since it's an ordinary folder, all photo management software (iPhoto, Aperture, Lightroom, etc.) can export to it without installing a plugin. (2) People can queue up photos to upload while traveling even if they're currently without Internet access. (3) Mobile clients are already built, and people can use the same client either to upload to my site or to send to their desktop for post-processing.
If you're running a site that people upload files to, I highly recommend integrating with Dropbox. They have an API, but I just did it by letting people share a new folder with firstname.lastname@example.org and pulling photos from that folder.
I wouldn't make it the only upload method, but I highly recommend it at least as an option. And with 25 million users, there's a good chance a lot of your new users already have Dropbox, especially within the early adopter crowd.