Per Rarst’s request, as an answer instead of comment :-):
The easiest way might be to create a third custom field, vote_diff, and order by that. You could use update_post_meta in a function to automatically calculate/enter the value of vote_diff when vote_up or vote_down changes. Where & how to do that will depend on where/how vote_up and vote_down are currently added/updated (plugin or theme or ….?).