Serge Zaitsev:

So, I ended up doing 80% of my work in terminals with tmux. But, the prefix thing? Pardonnez-moi, but usability matters. Pressing a chorded prefix hotkey only to press another chorded hotkey to perform a single action is clear nonsense.

With this in mind, I decided to customize my tmux to use only simple chorded hotkeys without a prefix for most common actions, and to make them easy to remember.

He shares his resulting tmux.conf and the reasoning behind the system he devised.