Though I'm really not the biggest fan of the simulation thing, I realize that it has always been (and always will be) a part of the series. So if I'm stuck with it, I might as well make the most of it. That being said, the idea of different simulation layers would be important for this story.
Since it's established that "lower resolution" layers of the simulation lead to more errors (gigalomania, reading steiner, etc.), I think it would be interesting to see a game take place on a layer that is much "lower resolution" than anything we've seen thus far. On the layer the bulk of the series takes place on, the errors we witness are more isolated and out of the view of the general public.
In this case, the layer would be so low resolution that errors would be commonplace. Universal laws and constants would break down, and conditions like gigalomania (and whatever else you could come up with) would be more frequent than not. I'm kind of envisioning something like the Zone from S.T.A.L.K.E.R., if anyone's familiar with that. In essence, there would be sporadic places and pockets in the world where things just don't make any sense. Time inversion, ripples into other layers, that sort of thing.
The world would be fairly chaotic. I imagine that the protagonist would be a character that was somehow flushed down to this lower layer from one higher up. He would meet a cast of zany characters, and together they would discover that their layer was doomed for one reason or another (corruption, culling, anything like that, etc.) and together they would work towards finding some means to escape to a higher layer.
Not really sure what you would want the gimmick to be for a game like this, and scientific technobabble isn't my forte either, but I'm sure you could come up with something. I think it would be cool to see some familiar concepts pushed closer to their limits. And don't worry, I'm sure we could somehow fit a Kurisu cameo in there somewhere /s
Maybe certain parts of the world would be completely fucked messes of time and space, with different eras of history smashing together like the Dreg Heap from Dark Souls 3 (underrated location imo). I think something like this would actually be a cool usage of the whole simulation thing. It never even has to be brought up that things are simulated by any of the characters, I'm sure you could come up with some in-universe terminology for layers.
Just something I've been thinking about. Hard sci-fi isn't really my area as a writer, I lean more on the Adventure part of Science Adventure.

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