The trouble is that what they change isn't necessarily the right thing. What needs to change is the generic formula for the filler episodes which usually go like this - Ash & co meet a new person. The new person has a pokemon. Team Rocket turn up and steal the pokemon & Pikachu. The group catch Team Rocket. Pikachu uses Thunderbolt. Team Rocket blasts off. Ash & co say goodbye to their new friend, promising to meet up again someday, although they never will.
I think that Misty could join the main cast again quite easily, so long as she finds someone competent to run the gym in her absence. The problem though is with what she can capture. Take the Kalos region - Ash has Froakie. It is a good assumption Serena will catch a water type, so let's say Clauncher. That leaves Skrelp and Binacle for Misty. One thing that the anime has been consistant with is that fish pokemon don't do so well on land, as shown many times by Misty's Horsea and Goldeen. This makes it unlikely that Skrelp would be seen much if she caught one.
Ok, so there are other pokemon from other regions that she could obtain - Slowpoke, Panpour, Ducklett, Wooper, Vaporeon and so forth, but this sort of negates the value of going to Kalos - why not just journey though the other regions and catch them there?
There is the potential for some of Misty's older pokemon to evolve, but Horsea & Goldeen are the most likely to & they'll still have the same problems with battling on land as before.
Psyduck is unlikely to evolve, Azurill certainly has the possibility of doing so, but after that the only real change that the old team could recieve is Gyarados mega-evolving. Unfortunately I am starting to think the chances of Ash ever getting a mega-stone are getting less and less, especially with the upcoming special for mega-evolutions seeming to suggest that for the most part mega-evolution will be a side story to the main series. And if Ash doesn't get a mega stone, I doubt that the rest of the cast would.