Once you start piling up some dependencies (vs. self-constained apps), I found homebrew more of a mess, while MacPorts more or less worked as I'd expect. The thing that drove me off Homebrew was dependency-hell with different versions of Python packages, while MacPorts pulled in the right versions of all the dependencies (it can even handle needing multiple versions of NLTK/SciPy/etc. installed in parallel, if different ports depend on them). This is perhaps the flipside of the reason many people prefer Homebrew: it tends to build against the base OSX stuff, while MacPorts tends to pull in its own parallel world of dependencies. IME the latter works more reliably, though it takes up more diskspace.
But, Debian's package management works better than either of them, so I've sort of been moving towards doing any kind of unixy work in a VM and treating OSX as just a desktop.