A specific open question is whether supporting 32-bit hardware and environments (including for example x32) is an important goal. While some communities, especially in the embedded space, currently rely on this, it comes at a significant cost and without significant advantage to other communities. We would like to attempt to address the needs of these communities within a 64-bit model to simplify things long-term, but this may prove impossible.
This is not just microcontrollers (hardly niche, but obviously different performance envelope), but also plenty of 32-bit Linux single-board computers (e.g. BeagleBoneBlack). Not to mention the earlier mention of endianess other than little.
on the other hand, rust does not support 32bit arm at tier1 either. https://forge.rust-lang.org/release/platform-support.html
golang so far still supports 32bit, but who knows for how long, after all it's Google who can do anything they want, plus golang is too fat for many embedded boards.
Thank goodness we will have C stick around for many decades in the long run, along with ash probably lua5.1 for scripting that is.
otherwise we need get rid of c++ for 32bit embedded fast.