Emacs. Runs as a server, stays alive when clients drop. Window management on keyboard. Tramp mode is great. But I'm sure you've heard this already :)
Iterm2 has tmux control mode support that enables somewhat native ui: https://iterm2.com/documentation-tmux-integration.html
There is also wezterm with its own mux server implementation: https://wezfurlong.org/wezterm/multiplexing.html
I'm using resurrect tmux plugin configured to rerun ssh commands, it's not perfect as it's not restoring remote session, but at least you have session open to right host in pane that you expect with scroll history.
Mosh is an amazing tool - https://mosh.org/
Does exactly what you describe with a minimum of fuss.
`wezterm ssh` uses ssh the way you describe it.
It does not offer persistence by itself, but iirc there are server components in wezterm which might give you reattach able sessions.
Ideally, I'd have my WM handle panes, layouts, etc. "Terminal multiplexing" seems to me to be misplacing client/UI concerns. Session persistence is the concern of the server, and multiplexing should be handled by ssh. However, getting the client terminals to coordinate nicely (e.g. reattaching to the appropriate sessions, opening new terminals in the same remote working directory) require more sophisticated clients than exist currently (to my knowledge).
Does anyone feel similarly? Anyone have a setup that approximates what I'm looking for?