I am agree with the fact of the WordPress API is limited, but there is no garentee that WP_Thumb will continue to work in further WordPress updates :/.
The image API will be, one day maybe, updated but for the moment you do not change your breakpoints, image sizes at any time in your website, the sizes are made on the conception of the website so you do not regenerate the images at any time. Plus the timthumb solution have opened security breaches on many websites and themes. It's safer to use the WordPress API, even is it is not complete.
The ultimate solution is to not generate the sizes when uploading an image but when you need it, so the ressources are preserved and the disk space. The plugin http://wordpress.org/extend/plugins/dynamic-image-resizer/ try to make this but there is a bug and the images are not quitely generated...
I hope there will be a real update on this point, especially because of the reponsive problem and the retina etc.