I’ve submitted another request targeted more towards my ultimate end goal.

If your intent is to have the new one, not the old one, make sure you close the old one, so the developer knows which you actually want.

Also, many shortcuts are unwise to re-program, so there are a limited number of custom shortcuts for users to work with in the first place. If you have a lot of Macros, you can run out of options pretty quickly.

However, reading between the lines, I think you may have misunderstood what I’m trying to do (and/or why I can’t do it right now): I want to assign the same shortcut to two S/R Macros that are always simultaneously “enabled” (i.e. active in shortcuts.xml), but configure one to only be effective when the other isn’t.

ICYMI: this is all based on the concept of the “In selection” configuration; while useful in many contexts, it effectively renders an S/R Macro useless unless something is selected. If you can configure an S/R Macro to only be effective when something is selected, wouldn’t you also want to configure a similar Macro to only be effective when something isn’t selected? Right now, NP++ doesn’t offer a way to do that, so that’s effectively what I’ve requested.

While Notepad++ has accumulated some bloat the developer has resisted going down the path of inventing and supporting a built in scripting language. Had that happened then it likely would have been easy to then map a keyboard shortcut to a built in script that had logic paths for the nature of the current selection, the contents, of the copy/paste buffer, etc.

I personally cannot see a situation in which your complicated “enable one disable the other via the menu” suggestion in the Feature Request would save any time or brain-space compared to having Ctrl+Key for one macro and Ctrl+Alt+Key for the other macro, and just remembering that “the one with Alt works on All text”. Personally, having to remember to go toggle both those macros in the menu to switch between them every time I wanted to change between All vs Selected would be more annoying to me than having two different keystrokes.

And if you, personally, are willing to do that extra step, why not just pull up the Shortcut Mapper instead, and remove the shortcut on one and enable it on the other?

Just my thoughts. (And, of course, you’re allowed to make any reasonable feature request you want; you just might want to be willing to consider alternatives, in case your FR is ignored or rejected.)

Prediction: This request will never be fulfilled.

Prediction: this dire prediction will not deter me from making reasonable requests in the future…

Macro-disabling functionality has been requested here

Prediction: This request will never be fulfilled.

there currently isn’t a way of configuring NP++ to disable a specific Macro as soon as something is selected?

Correct.
Macros in Notepad++ are really simple. And simple-minded.
If you want to open things up to scripting (programming), then you can do just about anything you want.

However, just to confirm: there currently isn’t a way of configuring NP++ to disable a specific Macro as soon as something is selected? That’s effectively what I’m trying to do, so perhaps I should have phrased the question that way.

for the same keyboard shortcut (i.e. apply the original Macro when nothing is selected, but apply the modified Macro when something is selected).

Not possible this way.
Make the macro use In selection (hopefully your search action is something that supports that option), and then to affect all text, do a Ctrl+a before running the macro.