For the record, until Campagnolo invented the derailleur in the 1930, racing bikes used in the Tour de France (among others) had flip-flop hubs with one side for the flats and the other side for the hills. So it's not a new idea at all and works just fine.

Chain slack for a fairly small difference in the cog sizes can be taken up in the sliding dropouts. Too big a difference and you'll need a chain tensioner in there.