Generative Design / Topology Optimization

I think when designing for FDM printing especially, print orientation must be taken into account to ensure that the part is at it's strongest to the stress path.

Yes... tensile & compressive loading is ideally parallel to layer buildup, whereas 'normal' to layer buildup will net weaker parts.

Is 5D printing the answer to manufacturing your parts, https://www.youtube.com/watch?v=5z2dk0H5mZU

This should eliminate the downsides stated above, right?

If you could micro-manage layer construction to that degree, I guess you could.

However, if your design is teetering the edge of reliability... then the effort is better spent (IMO) designing to a more conservative safety factor.