I would love to see some groundbreaking game where a lot of old awesome characters appear to save a region or something. For me the most epic story line where I genuinely felt the game world was in danger was the Hoenn one, with all that extreme weather and what not, closely followed by Unova (B/W not B2/W2, none of this flying ice ship crap) & Sinnoh. So in an ideal world I would love some story line where the region was in real danger where everyone is there to help, and the new protagonist gets to fight alongside N, Gold, May, Wallace you name it, with assistance from Oak, Elm, Juniper, Birch, Bianca and whoever else against some of the old evil forces like Giovanni or Silver, maybe even Gary/Blue could appear, particularly if Oak comes back as well! Something that really puts a mark on all the awesome games and characters there has been, that would be a real treat for long term players, and the old protagonists could be with their respective legendaries (like how N appears in B2/W2) etc etc.
More realistically though, hasn't Crasher Wake appeared quite a few times lately? He could be involved again, I quite like him anyway.