So doing some research on everything (who's behind it, what is known, what has gone under the radar, what was posted here, etc.), this is just my theory on some of what Zwei may be about. Chalk it up to putting current pieces of a puzzle together.
A great help for this was an old "Staff" list on the Tango website. It was taken down before Project Zwei was announced, but you can use the Wayback machine to view it. It also has given me more confidence this game may turn out to be amazing, as almost literally everyone involved are talented individuals (some forming an all-star casts) that looking more into things like their portfolios, twitter, etc., are very evidently passionate about horror and the disturbed. Helping is director Ikumi Nakamura, who helped work on Bayonetta and some other titles and seems to have a passion for odd and disturbing imagery and horror games, based on things like her Twitter feed, and apparently for some some 'reason' went on a trip with other Tango members a month ago to areas in Japan known to be cursed/in ruin, and seemed to be especially excited to be visiting a place that is associated with Silent Hill.
I think it may be best to tackle this one category at a time.
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Project Zwei is almost certainly going to feature gunplay. There are some big gun ethusiasts on-board, recent images of them practicing gun animations, they seem to have a lot of models of weapons in their office, interested in hiring people trained in FPS/TPS gameplay, and to top this off, Mikami has a thing for trained professionals with firearms being the leads of his horror stories, so it would logically make sense.
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The game is set in an ocean-side town or island that seems to experience frequent flooding and has been overgrown. This one seems obvious in retrospective, but an on-going theme noticed in the concept art and the one in-game screen you can partially see is overgrowth and water. In a piece of concept art, you can see a decaying ship at bay, a lighthouse, and the ocean, but in a lot of concept art you can see water on the floor, or water damage. There also seems to have bee no-care left for any of the structures, and plants have ravaged and taken over buildings.
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The monsters seem to have human qualities, but are decidedly not human (or at least, no longer). Pay attention to the following images:
The monsters, at least these, seem to have human qualities about them. They seem to be doing human-like tasks; Using tools, collecting water, some even seem to adorn some clothing. These may have been human once, and it is true that the structures around the environment are man-made. There's even concept art of a human.
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The game's story involves slavery and an old slave-driven society. My theory is that this area is an isolated island, and was once an island of slavery plantations, and the like. The one character we have concept art for is black, the ship we see in concept art is a slavery ship, and there is some concept art of what looks to be an abandoned plantation (not to mention it fits the theme of plants overgrowing the land). I am guessing these monsters were once human, but something happened.
This also would explain the bug-theme if this was an island for plantation, as any farmer can tell you, one of the biggest threats to plantations or any sort of farmland is insects. This would also imply that there is mutation going on, supported by the beast at play here. Cause an exact effects unknown. Was it natural causes, a curse, experimenting, something else? No clue, that's up to theorizing.
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Our characters sanity may be in question. There was an old build of Resident Evil 4 that involved the question if Leon was sane or not. Some of the art, both prior to and before the announcement of Zwei, looks a bit surreal, even considering if mutation is gong on here. However, there seems to be people on-board in the project which have a deep interest in human psychology and disturbing imagery/abstract art. Some choice messages made from staff (mainly on Twitter) since Project Zwei was revealed had one thing in common in passing, there almost seemed to be an in-joke about going insane on the project. Back this up with the psychology stuff, the love with people in the team for the disturbed and the abstract, and the fact the last horror game Mikami almost made was supposed to have a theme of insanity, backed with some of the stranger concept art, and I believe our main hero may be having delusions and cases of insanity himself.
What I can piece together for now.