Maybe it's gimmicky, but I feel like you could get some interesting form factors with the CPU and GPU cards sitting back-to-back or side-by-side, and there would be more flexibility for how to make space for a large air cooler, or take it up again if you've got an AIO.
I know some of this already happens with SFF builds that use a Mini-ITX motherboard + ribbon cable to the GPU, but it's always been a little awkward with Mini-ITX being a 170mm square, and high end GPUs being only 137mm wide but up to 300mm in length.