I gave up on tmux on my Mac, as I mainly used it with teamocil to have saved layouts of panes and commands, but I never disconnected from it. I found quite a few people use it this way.
I wrote iTermocil[2] to replicate the functionality of teamocil natively in iTerm2, so I could have all the upsides (from my POV) but keep native UI elements etc.
Simple because I came across teamocil first, as someone recommended it to me. It is actually teamocil that led me to tmux!
I have since come across tmuxinator, which is almost identical, but from my reading of tmuxinators docs it seems it is more flexible in how you can configure it.
I wrote iTermocil[2] to replicate the functionality of teamocil natively in iTerm2, so I could have all the upsides (from my POV) but keep native UI elements etc.
[1] https://github.com/TomAnthony/itermocil