Apart from new variations/expansions (hub, story, single-player, maps, graphics, characters, abilities, leveling rewards, weapons, clothes, yada yada), they could experiment with some of the traditional design elements, such as some maps no longer being symmetrical, or gameplay mechanics such as being able to collect and use items strewn around the map (although this is kinda what Clam Blitz is) or tactical co-op gimmicks (being able to jump on your teammates to reach higher ground, etc).
In general, they could make Inkopolis bigger and more immersive, with more things to discover, unlock, and interact with -- maybe even a town that's a live online hang-out area with chat options.
They could also introduce under-ink sections of maps, provided they can make the swimming physics simple and intuitive.