You say "think about it, it's never been done before", but there's a good reason for that - it looks terrible most of the time. Pokemon does differentiate its locations but the style doesn't change, every single location in each game is cohesive with that game's style. It might works for horror games where unusual, disjointed and unsettling art styles are part of what the game uses to create an atmosphere of unease, but the best horror games usually have custom-made art to get the maximum effect out of this. If you buy a Time Fantasy pack and stick MV RTP characters on it, or have one city rendered in the Pop Horror style and another in the DS/FES tiles, it's going to look bad because the way each of those styles uses pixel clusters, palettes and sizes is entirely different and they're not going to mesh. There's a certain amount you can get away with, the DS/FES character sprites on RTP tiles because they're close enough to work, but if you're thinking of having wildly different resource packs for each area in your game, don't do it.
I think you also need to separate a game's style from its individual elements. Take something like Fire Emblem Awakening or Fates, for example. In battles, the characters are represented by sprites on a 3D background, while combat is fully rendered in 3D with character models. Portraits are hand-drawn. Those are all disparate elements, but they tie together to make the game's "style". The individual elements are different to each other, but are consistent with themselves. Each sprite fits the same pattern. The battle maps are all rendered the same way. The portraits are easily recognisable as fitting their own style. Now, if suddenly one map looked like it was built out of tiles from the GBA Fire Emblem games, or a character showed up with a portrait done in a hyper-realistic life drawing style, that would be a serious style break because it's going against the previously-established combination of elements that makes up the look of the game.
