I'm not 100% positive I understand the objective, but I think I have the basics down: You want one activation key to work in many apps, and you want to use the same simple keyboard shortcuts for those actions, regardless of which app (or site) might be active when you trigger the macro.
If that's what you're trying to do, I'm not sure of the best way to do it, but here's how I would personally do it:
I'd create a macro group for all the shortcuts I want to use, and that macro group would be active in all applications. I'd set up that group to show a palette of macros when triggered by some hot key (not a typable key combo). This prevents you losing actual typed characters at any point.
For example, here's the macro group I use to present a list HTML snippets I use often in my day job:
When I press the hot key, I see the palette:

I press A through E, and the text is inserted and the palette vanishes. This works because each macro in the group is assigned a single-letter hot key, and those keys only work when the palette is onscreen.
In your case, you want to have multiple entries for many of the letters. You could create duplicate macros, all assigned to the same letter, which would then force a conflict palette to appear when you typed that letter.
For example, I added a new "A" shortcut to my palette, and activated the palette:

If I press A now, the conflict palette appears:

I'd then have to type more characters until the right macro is chosen, and that's a pain. So instead, what I would do, is build logic into each of the single-letter macros. That logic would use the rules you've defined above to determine which actions to take.
Say you have an "A" action, and you want it to do one thing when in YouTube in Chrome, and something completely different when in Mail. In the A macro, build logic around whatever you can uniquely identify about each use case. In pseudo-code, something like this would happen after you trigger "A" on the palette:
"A" macro launches
Within "A" macro
Case [frontmost app is Mail]
Run YouTube-specific macro to handle multiple possible tasks
Case [frontmost app is Chrome]
Run Chrome-specific macro to handle multiple possible tasks
Case etc...
End "A" macro
You could, of course, have the actions themselves within the "A" macro (instead of launching other macros), but it might get very messy and crowded if you have lots of actions with lots of conditions with lots of apps, all buried in one macro.
For troubleshooting and easy updating, I prefer to keep the modules short and sweet. That way, if you have 15 tasks assigned to "A," and you want to edit the Chrome tasks, you don't have to find Chrome's section in your massive macro, you just edit the called Chrome macro.
Does that make sense?
-rob.