You can also use <C-C> to quit command mode instead (and this one works in keymaps). It also works in Insert mode but doesn't trigger the InsertLeave event, which might upset some plugins.

As far as I know the character pending mode thing that r does is a bit unique in that it isn't insert mode, but also not quite replace or operator pending mode. If there's a way to remap any key to work with r then I'm not aware of it.

Have you considered instead remapping <Esc> on an OS level? The XKB option caps:escape turns your Caps Lock key into an additional Escape key, which is even easier to type than <C-Space>.

For the r case I think you need to set the mapping in "operator pending" mode, which you get by putting "o" in the same position you already have "!".

I don't know what the issue is with command mode.

There is plenty of precedent for custom escape bindings, often using jk or jj. You might be able to find examples to get an idea of the best way to set up those bindings.

There might be an issue with <C-space> in particular if it has existing mappings in certain modes. I know that auto-complete plugins often use that mapping to make the completions menu appear. There might be some interaction with that mapping specifically with plugins you're using, or with built-in behavior. I suggest experimenting with a different mapping to narrow down whether problems are due to the way you are writing mappings, or to a specific interaction with that key sequence.