We are all used to many compromises in the name of tire clearance for fatbikes. Asymmetric builds, extrawide bottom brackets with ridiculous Q factor, custom, limited drivetrains… these have become the norm.
The reason we make these designs sacrifices is to accommodate the chainline issues created by the easiest gear ratios possible. The easiest your ratio is, of course, the little chainring/big cassette gear ratio. With a standard bike drivetrain, that gear ratio puts the chain closest to the tire at both the bottom bracket and the hub. That is what generates the need for design compromises.
An inverted crankset wouldn’t work–the big ring would hit the seatstay. But what about an inverted cassette (and reverse parallelogram derailleur)?
You’d be cross-chained in little/big (lowest gear) which is a potential issue. Cross-chaining isn’t so horrible anymore, though. Look at the chainline on SRAM’s XX1 with a lot of builds.
You’d be putting a lot of stress on the outside of the hub, certainly…but with most cassettes having the lowest 4-5 gears as one assembly, that shouldn’t be an issue either.
Chainstay clearance doesn’t look to be an issue on most fatties.
Big/little (your fastest gear) would simply index into the rim, but the chainline would clear the tire because you’d be in the outboard chainring position.
Little/little might not be possible…but so what?
It might be a creative way to work around a standard bottom bracket and a fat tire. Maybe.