The reason that Homebrew defaults to /usr/local is because there are a lot of braindead packages out there that hardcode the possible locations for software (e.g. /usr/lib and /usr/local/lib), and if you install Homebrew somewhere else, you can't use Homebrew to satisfy the dependencies of any such braindead software you come across.
However, if everything you're installing that depends on Homebrew-provided software is also installed through Homebrew, then it should work regardless of location (I say "should" because I suspect that not every single Homebrew formula has actually been tested with a non-/usr/local install path).
Personally, I stick with /usr/local both because I've never had a problem with it, and because that makes it easier when working with software that uses a default PATH (since /usr/local is usually put in these default PATHs). But if you have any concerns whatsoever, then by all means use a different install prefix.
That's a really weak justification. For most of those "braindead" packages, it is actually fairly easy to get them to install into arbitrary locations. After all, both Fink and MacPort have been doing that with great success for over a decade.
Sadly, you are correct about "not every single Homebrew formula has actually been tested with a non-/usr/local install path". In fact, while there are many Homebrew formulas of great quality, my impression is that there are also m many of rather poor quality, with other problems in them. E.g. just yesterday, I discovered that the Homebreak lmdb formula does not build properly versioned shared libraries -- because upstream didn't, and the packager either didn't notice or didn't care to fix it
I rarely (if ever) this kind of issue with MacPort and Fink, which try hard to avoid such problems (at the cost of a higher entry barrier for packagers -- for better or worse). Mind you, I am not everything is golden with them, either.
Disclaimer: I've been involved with the Fink project since OS X 10.1 or so.
However, if everything you're installing that depends on Homebrew-provided software is also installed through Homebrew, then it should work regardless of location (I say "should" because I suspect that not every single Homebrew formula has actually been tested with a non-/usr/local install path).
Personally, I stick with /usr/local both because I've never had a problem with it, and because that makes it easier when working with software that uses a default PATH (since /usr/local is usually put in these default PATHs). But if you have any concerns whatsoever, then by all means use a different install prefix.