I currently use MacPorts... just wondering why I should switch?
FWIW, I was an early Homebrew user and even contributed a few recipes, but I moved back to MacPorts because (and no offense to mxcl, but it's kind of unavoidable) the author seems to do things with little understanding of the underlying system or justification. Taking ownership of /user/local is completely utterly pointless and just plain bad advice. Copy-and-pasting optimization code from the Gentoo wiki is pointles…
I can't say I've had any problems with compiling Ruby gems against homebrew besides some settings that needed to be overridden in the MySQL gem, so that hasn't been a problem for me.
I kind of have mixed feelings about the ownership. So far I've been running it in /usr/local owned by my user and haven't had any problems, but I can see the security argument for not doing it. It doesn't feel any different then compiling your own binaries and leaving them in your home directory, something I've had to do on several hosts I've had in the past. (Also: Snow Leopard doesn't install anything to /usr/local by default, so if you're starting from scratch there's nothing to take ownership of...)
Overall, I've rather liked it so far. We'll see if I regret it...