Portal 2 ended with Chell's story finally coming to a conclusion, her rising to the surface to greet a world torn apart. It's ambiguous as to when this takes place, whether long after the events of Half-Life 2 or around the same time, but it's clear that Chell's story is now over. She escaped. Dragging her back for a sequel would undermine that. There's far more potential for Portal 3 to explore co-op or Aperture, rather than dredging back up this silent protagonist and her cool fall damage negating boots.
It feels like a pipe dream asking for another Portal, but for the longest time, that's how it felt with Half-Life before Alyx as well, so perhaps it's not too much to dream for a sequel. The FPS formula lends itself nicely to VR and Alyx was the definitive proof of that, transforming bog-standard gunfights into high-octane, immersive battles that had you scrambling for cover while you swapped out the magazine for a few more shots. It inadvertently made going back to an FPS with a controller or mouse and keyboard feel lacking. However, Portal wouldn't work in the VR format. Sickening nausea from leaping across rooms or zapping from one point to another would be overwhelming.
In that regard, Portal is the perfect counterpart to Valve's VR push to still let people enjoy the world of Half-Life. While the main story of the game ventures into the medium of virtual reality, we can perhaps explore that world more outside of the headset in a Portal sequel. That's why it should be followed upon, at any rate, but Chell? Chell is done. Her successor could be the two robots, or it could be a new test subject altogether. There's a wealth of opportunities for Valve to bring someone new into the fold, to create a new character, but the issue comes with treading on the old ground. GLaDOS reset could end up in a narrative akin to the first Portal, and after such a long wait, that would be a tad disappointing.
The hook could then be the gameplay once more as it was in that first title. But rather than 3D puzzle platforming, it should be co-op as we got in the second. Portal 2 is still undefeated in its co-operative level design, and having an entire game dedicated solely to that very design would be the perfect opportunity to expand upon the series further, to take it back to its roots as a fun gameplay-oriented title with the odd story beat here and there to offer an incentive for pushing forward. We could see the two that we grew to love return or we could get new 'faces,' and it would work perfectly as a sequel given GLaDOS being reset, the lack of remaining test subjects, and the need to test.
Alternatively, we could see the portal gun in the real world and start with a new character finding this revolutionary Aperture tech - maybe even stealing it from GLaDOS - and have a hybrid between Half-Life and the puzzle platformer. It would be intriguing to see how the gameplay mechanics would operate in a more open environment that isn't catered toward it, at least not in-universe. In doing so, Valve would also build upon that idea of providing a Half-Life counterpart for non-VR players. It would also be a monumental shift in the series and bring something completely new to the table, and after so long waiting, that's exactly what it needs. Alyx excelled because of that, stepping out of the series' comfort zone to do new things.
The point is that, whatever it ends up being that Valve does with Portal, if anything, it shouldn't entail Chell. Her journey was inextricably tied to GLaDOS and the two parting ways in the finale, ending their story, was a perfect moment of closure that tied the knot on two brilliant titles. Her returning would undercut that tightly bound connection and narrative, and sully that bittersweet finale. But, that's not to say that there's no potential in a sequel. On the contrary, there are too many ideas to put to paper.