I suspect only very high end games, image processing apps and that kind of thing would ever need to care about the order of fields in a struct... perhaps the author of my web server as well, but even that only if I have a ridiculously high load on my server (which I don't, almost no one does).
So, no I don't think I should know that until I develop one of those highly niche applications myself.
If you have an algorithm with quadratic or higher complexity somewhere you will be in the millions even if you only have a few thousand entries to deal with. Now the worst case cache miss (down to ram) is modeled as roughly 1000 cycles. Put that right in the middle of that O(n^2) algorithm and your web app will be able to handle 1 request per second on a good day.
Note: that calculation is extremely simplified
And even if you do quadratic operations in your handler, how often do you write a new such handler? Most of the time you work on stuff around that, supporting infra, testing, etc. None of those needs to be cache optimized either.
It was mostly meant as a example of millions of operations even at a small scale. Sadly I have seen way too much accidental O(n^3) code and not all of it could be "fixed" trivially.
> This has nothing to do with caches.
Would you rather handle 1000 request per second or 1? Caching has the potential to make an already bad situation so much worse.
> how often do you write a new such handler?
You only need to write one to DoS your server.
Would you rather like to approach this problem by optimizing memory layout which, let's be honest, tends to give you more in the region of 1-10% improvements rather than 10-100x, or would you rather like to try to go from O(n^3) to O(n^2) or O(n log n) or similar?
The real meat is in the complexity class. Cache effects are where you go when there is nothing else to optimize and it actually matters. Preemptively making all your data structures 2-3 as big because of not-actually-necessary padding does not sound right to me, but YMMV.
While you are optimizing your struct layout and decrease you app start time from 1.122765 seconds to 1.122764 seconds, I ship production code at 2x the rate because I only optimize for performance where it matters while otherwise optimizing for maintainability, testability, extensibility, dev fun and actually shipping.