So, as revealed by the Arkham Nights news item, another expansion lies on the horizon. I'll admit it: I doubted that they would continue, since Miskatonic seemed so much like a final, all-inclusive expansion. But I was proven wrong! And so, we must baselessly speculate on what the expansion will include, for that is the way of the forums. Possibly. I don't know, feel free to speculate if you want.
My contribution: up until Miskatonic, everything was pretty formulaic. You had big boxes, which each had a new board, new mechanics, and a whole bunch of new investigators and AOs, ad you had small boxes, which had a herald and a new mechanic, with both varieties having many cards of various kinds. But Miskatonic bucked the traditional trend for big boxes, with no investigatoes, AOs, or board (not to imply it was a disappointment in any sense of the word). I believe we'll see some more major mix-ups in the formula. Specifically, we will see a steering away from certain game mechanics. With Miskatonic, the designers seemed to think that we had enough AOs, investigators, and boards, and so focused on other areas. Now, I suspect the designers will think that we have enough Location, Gate, and Mythos cards and not include any of those (the first expansion not to do so). Instead, they will focus on something different. My guess is a whole bunch of new Guardians, Heralds, and Institutions, as well as at least one new card deck. Or that's what I'd want, anyway...