If GF took the plunge and made a real time action game spinoff, or maybe a low delay RPG like KOTOR, they might have a huge success. Perhaps even a Wii U system seller.
I doubt they will make them again. PBR got bad reviews and both Colosseum and XD only sold about two million copies together versus Ruby and Sapphire which sold 16 million copies of the game along with the six million copies that Pokemon Emerald sold.
The thing is, Pokemon is now a sufficiently long-running franchise that a significant fraction of its audience are university-age and older. But so far GameFreak doesn't seem to have realised this - why else would we have two Mega Charizards, two Mega Mewtwos, and Pokemon Origins coming round the corner? It's a genwunner's wet dream, seemingly there only to hook back in people who played back in the nineties and who have fond memories. I've not ruled out remakes of the gen I remakes either...
But that shouldn't be the way GameFreak tries to attract young adults. (WHAT?) Pokemon is evolving, constantly, and just regressing to Gen I stuff is not the way to go. Look at New Super Mario Bros, which is basically the same thing applied to everyone's favourite plumber, and which was first released about 20 years into Mario's career, a milestone Pokemon is now approaching. The games all sell like hot cakes, and they are quite fun even, but what was the best Mario game on the Wii? I'd reckon 90% of people who had played them would say Galaxy 1 or 2 and very few people would even mention NSMBW.
So, basically, we should be hoping that GameFreak continues to attract mature players, but not in such a backward-looking way. It should also acknowledge that the people who have played it from the beginning have grown up and want something with, for example, some actual challenge. A Colosseum-style game that was attractive to adults would probably outperform its predecessors (which didn't have shabby sales, you know, 2 million each is not bad) because the audience is there. Wii U sales have skyrocketed recently with the Mario Kart 8 boom, and the future may look brighter for the console after E3, so even that may become less problematic than it is at the moment.