Watching the Andrew Kelly video mentioned above, really drives home the point that even if your compiler automatically optimizes structure ordering, to minimize padding and alignment issues, it can't fix other higher-level decisions. An example being, using two separate lists of structs to maintain their state data, rather than a single list with each struct having an enum to record its state.
AOT'd languages could re-arrange a struct for better locality however the majority (if not all) languages rigidly require the fields are laid out in the order defined for various reasons.
The as-if rule gives an escape hatch, although in practice it is hard to take advantage of, especially without whole program optimization.
All of these things boil down to combinatorial optimization problems (bin packing ring a bell?). And there are no widely available compilers or JITs or whatever that bundle ILP solvers. Thus, what you're really getting with every compiler is a heuristic/approximate solution (to many many combinatorial optimization problems). Decide for yourself whether you're comfortable with your code just being approximately good or if you need to actually understand how your system works.