I probably would have preferred it if the Hidden People arc had just been left after the first game, to preserve the sense of complete mystery; believe me, the way they wrapped it up was a damn good one, and I loved the whole story regarding the astronauts, the lunar ray and - of course - the sasquatch, but it did slightly ruin the 'dumbfounded' effect the first game had on me. So the "new game, new mystery" idea sounds good to me.
It's also worth noting that Grickle had invented the Hidden People before
Puzzle Agent came out, meaning they're not afraid to experiment with their current characters and have therefore got A LOT of source material to use (here's hoping that Principal Skeleton does play a part in the next one).
Personally, I'd like to see more of the eerie 'Madness' that undoubtedly comprises the majority of Grickle's short videos, and that we briefly saw in the first game. There's just something about it that genuinely creeps me out, quite a lot, even if it is portrayed through hectic monkey noises. Of course, explaining it fully like with the Hidden People might ruin the effect, but if they could make a game or two centred around it that left you in the same complete suspense present at the end of the first game then that would be great