I also use C-s on my local machine because:

1. I can still use C-a with readline (go to first character)

2. If I ssh and then use screen, I can use C-a to navigate my remote screen and C-s to navigate my local tmux.

3. C-s is closer to C-a then other letters on my keyboard.

C-a still works with readline. You just need to C-a first to 'escape' tmux and then C-a again. Actually just hold ctrl and hit 'a' twice.

C-s will suspend the terminal on some platforms. (Which can be resumed by C-q.)

Because C-a already does something useful.

I assume ctrl-s is easier to press than ctrl-a, I have trouble with ctrl-a on Mac with reconfigured CapsLock, and my bind key is ctrl-space.

That's why I remap the right alt key on mac (laptops) to ctrl. Having left right balanced ctrl keys is much more important for my workflow.

For a while I ran a setup where I did all of my work in a local tmux session, but part of this work involved SSH-ing and attaching to a screen session.

When using both, especially nested, I found it beneficial to have a different leader for each.

I also use <^-a> to go to the start of the line, so I'd miss that.

I use `bind a send-prefix` and do a `<^-a> a` to make up for the bind :)