I would suggest checking against the corpus before saying "x should be enough for anyone". There are also occasional but valid uses for non-standard sizes.
Perhaps generate the standard thumbnail sizes at upload time and then generate and cache tumbnails of non-standard times until they haven't been accessed for a few days.
Doesn't take up much space, like just deleting all the thumbnails that are generated, and it saves time down the road as the most common thumbnails are already generated.
I wouldn't rely too much on the Squids. They do an excellent job, but thinking of those of us who use Mediawiki outside the foundation, I would much rather see an intelligent thumbnail generating and caching scheme that doesn't rely on Squid being present.
Thank you, Derric Atzrott