Like I said, Homebrew installs in its own directory pretty well. I chose /usr/homebrew, explicitly so I can rm -rf. I think for most Homebrew users their Macs have nothing else in /usr/local and so that's why it's not an unreasonable default.

Changing the prefix still doesn't mean that each app is sandboxed. That is what the parent comment was talking about.

You can't do rm -rf /usr/homebrew/$SOMEAPP/ and know that it is all gone.

Homebrew actually uses /usr/local/Cellar, so rm -Rf /usr/local/Cellar/pypy is what you'd want, except that it won't remove symlinks to /usr/bin, launch scripts and such; you still need some kind of uninstall script (brew uninstall).