How about a Kanto Sequel in the 2016 Game?
Johto is included, but you start again in Kanto, let's say 20 years after the Events of the original R/B.
With new Cities, changes in Gym Leadership and Top 4 Members, the Region has become lager and more popular than ever before. Due the huge Wave of Tourism from Trainers of other Regions, non-native Pokémon and Mega-Evolution have found their Way to get there.
As for the Threat, let's go back to the basics: A evil Group is trying to make use from the Tourism to have easy opportunities to steal Pokémon from all over the World in one Region. Their Members infiltrated many public Services and other Locations where lot's of People and Tourists are. At First there's a small Number of Complaints, but as you progress trough the Story, those complaints not only become bigger in Number, but also more severe, as far as some Mega-Stones also got stolen. Each City got their own "Mini-Boss" with a Mega-Pokémon that you've got to beat, and in the End, just before you face the Pokémon League, you'll meet the big Boss, who personally wanted to take care of the strong Trainers who gathered there.
To make the Story extra meaty, a second Storyline reveals itself when you complete the Nationaldex (wich should be 150 again), that the Guy you have beaten was actually the Vice-Boss. The true Boss has stolen Prof. Oaks Research Data of eveything he had, including the Pokémon Data you collected from him and is intending to sell it to other organizations across the Globe. He fled to Johto, and you have to chase him. But here you have to deal with Grunts from every Region from the Main Series, all working together to stop you, since they all know by know how dangerous a small Kid can be. At the End you Face off against every Boss from every Team, and at the very End you have the final encounter with the Big Boss, who at that Point should be equally as powerful as Red on Mt. Silver was.
Well that would be my attempt on a Game celebrating the 20th Anniversary of the Pokémon Franchise. How does it sound to you Guys?