Personally as far as speculation of how will new games impact pokemon series go. Given how were approaching 20 years of pokemon franchise existence and according to Junichi Masuda "new games will tie everything together in unique way".
Whatever that ambiguous statement could mean.
I am hoping how we wont be seeing yet again complete revamp with Ash dumping everyone and getting another set of new companions. Who will become wasted potential replaced after 3 to 4 years never to be heard from again.
Such approach only defeats point of what this show is supposed to be about. And that is friendship, consistent adventure which is supposed to evolve and build on itself and presence of strong continuity. Which only lose every point if complete sweeps are done all the time.
Perhaps in align with 20 year anniversary and alleged surprises new games will bring on table perhaps status quo finally gets break with either one of Ash current traveling friends continuing with him on next adventure. Be it Clemont, Bonnier or Serena.
Or we see one of Ash friends from past returning to anime becoming significant to storyline again.
Because looking back why not for change keep one of current traveling companions and bring one of olders back receiving sequel to its own story? Many of ex main characters have unfinished things worth to expand upon.
Taking advantage of history and friendship which there exists between Ash and older companion bringing more stable continuity based story. Following tougher, experienced and with basics covered traveling companion who is ready to step up and go on bigger, more challenging growth, introspection of his own feelings and emotions, more engaging battles and more complex storyline.
And since Sun and Moon games from looks of it will be based on Hawaii taking place in tropical environment provides stable and solid groundwork on which lot of water themes could be explored creating entirely new and original quest around it. Provide required logistic support to feature often neglected aquatic species which cant maneuver that much on land and deliver new ways of utilizing pokemon in battles and ways of developing character.
With water as type having so much diversity, mystery and options to work with. Especially in becoming type which has been paired with any other pokemon type out there(including fire) representing element which is essential for life(water). Thus offering material for eventful and gratifying story arc.
So for that reason I cannot help but think how Misty being involved with such region would make lot of sense. Because admittedly I would welcome see her rejoin Ash for adventure through such region. Just think about all possibilities and novelties through which her story could be pushed forward. In making more substantial progress in becoming water pokemon master and one day E4 member living up to her idol Lorelei?
We could see her learning how to understand better pokemon feelings understanding their true nature like manga did with Suicune who choose her as partner leading to possible mega evolution of her Gyarados, find out about Misty parents, why she fears bugs, understanding how to be more authoritative and understanding toward Psyduck training it to become usable battler etc; so much potential to do more with her character ).
Have Misty demonstrate how much she learned at gym utilizing acquired skills in different activities. Such as water sports, tournaments in facing seasoned type experts, under water battles(which never disappoint being amazing like one Misty had vs Molly in third movie) which could be turned in chain of competitions serving as follow up from what Whirl Cup established about legend of water masters. Etc, etc.
Not to mention after not seeing Ash for so long it would be interesting in least hand to see how they would react about each other. Retelling on past adventures, revive that lighthearted banter and teasing, spirited nature and lot of humor and lively dynamic between them.
Enjoying and missing her rather wide palette of emotions and strong presence being worth to see how she could affect anime nowadays if new plots are present behind her with point of pushing her in reaching new heights as trainer.
Perhaps best solution lies in killing 2 birds with one stone. In both keeping Serena for next generation doing new things with purpose of making character reach new depths and bringing Misty back. Something many fans hoped for. Having for change two more experienced and older girls in main cast ccreating surface for entertaining, vivacious and meaningful dynamic. Since Serena would be meeting one of Ash older friends learning more about his past and form conditions under which both girls would work for becoming good friends as journey gradually unfolds out.
EDIT: Pipe dream I know, but nonetheless I would welcome it.