Mac only: Open source media player Cog aims to be the anti-iTunes: it is a simple, one-playlist, folder-browsing media player for OS X that supports many features missing from iTunes, including global hotkeys, Last.fm, and FLAC and Ogg Vorbis support.
Music junkies looking for a library manager similar to iTunes will probably not be happy with Cog, but Mac users looking for something more akin to previously mentioned Foobar2000 will be quite pleased. It certainly isn't as feature filled as Foobar, but the organisation is somewhat similar. Cog is basically a "Now Playing"-type window, which you can drag songs to and from through a file browsing pane. Instead of having an always-loaded library, you actually search through your music files on your hard drive and create quick playlists with those.
Cog supports a huge amount of file types, including the open source, as-yet-to-be-supported-in-iTunes FLAC and Ogg Vorbis, among others (though it doesn't support metadata for AAC files, which is strangely too "anti-iTunes"). It also supports M3U and PLS playlists, for those playlists you want to have on hand for quick generation (though again, they'd be stored on your hard drive, not in a library within the app). It also supports Growl, the Last.fm plugin and global hotkeys, which of course you can map to your Mac's media keys.
Cog does not edit metadata, though it can read many different types. Thus, you would need to whip your metadata into shape using other applications, but they're so powerful that it's almost not a problem (it's not like you'd have to have them open all the time). It's certainly not the way many people are used to listening to music, but if you'd like an app that uses half the resources of iTunes, Cog is a great way to do so while trying something a little different.
Cog is a free download for Mac OS X. Development is a little slow, but the app is definitely usable, and the nightly builds provide a new look, a few more features and a lot of fixes if you find yourself having issues (although I have yet to, and I'm still running the quite old stable version).