I think (and I could be wrong) that the biggest difference is the RAM. Not important as regards to file size, but to database size. If you get too many tracks on there, it can become an issue.
Don't forget caching. If you've got a lot of Flac on your player, you'll need all the caching you can get. You'll probably find that a Mark 2 is unable to spin its disks down at all when playing Flac. (Mind you, you might find that with a Mark 2a too; I haven't tried.)

Peter