-People would not be able to get used to split Marts/centers after gen 5. While they would be remakes, they would have to retcon things to put them together.
-They would need an explanation for the gyms getting special buildings when it was a more unified look when the games take place in the canon.
-Getting people used to the region would be great with sequels that are more focused plot wise, ala Unova. I know that sounds sad, but lets face it, kids of today would be fucking lost unlike the kids we were 10 years ago.
-Sequels would allow mossdeep to get numbed. Another factor that remakes would be bad for. Mossdeep was a freaking difficulty curve from hell, and emulating it would be brutal.
On the downside, new characters would be introduced, as Brendan/May would be 18 or so in the current time span, let alone any future time spans.