I think if you're going to go down the road of starting new each region, you might as well make a bunch of smaller "episodic" games instead, one game per region. It breaks up the workload, you get something out faster than trying to do it all at once, and it works just as well as "somehow I decided not to take my faithful Dragonite with me". You can have an overarching story if you want, or just some references like recurring characters, but the transition between regions is an excellent place for chapter breaks.
There's no other way to do multiple regions (especially "all" regions) while keeping it relatively sensible. Either you power up successive regions, which can lead to Bug Catchers having level 150 mons, or you start fresh each time. It's just not at all reasonable to offer regions with wild Pokémon all in their 80s and have it look like any kind of place we'd recognise. So really, we're stuck with the starting from scratch option (although it's fine to unlock the previous regions' Pokémon upon beating the Elite Four).
Does anyone else have any ideas on how to actually implement "all four/five regions"? How about preferences?