The speedup is very noticeable. Like others I'm running the "native-comp" branch of Emacs, since months, without any issue.
It's now been merged into trunk and it's going to be the default:
https://news.ycombinator.com/item?id=26935401
The only drawback I saw is that compiling Emacs itself takes 3x to 4x longer when compiling the native-comp branch.
I tried this on macOS a few months ago and it was pretty rocky just getting the thing compiled. I tried again last night and it pretty much Just Worked(tm) thanks to this[1] project.
Note: this was on an Intel mac; anyone with an M1 tried this yet?
I did run into some problems with some newer packages on the GNU ELPA. (Specifically consult, marginalia, and vertico by github.com/minad) Straight.el complained about not being able to find the packages. Any suggestions on what I might try to fix this?