Yes, Wine works, even for newer .NET Framework 4.0 games, after having gotten the prefix set up previously. The only distribution of Wine that I've gotten running is the Homebrew --devel version, which as of this writing is 1.7.47. MacPorts should work as well. Basically any port that installs or symlinks the entire tree into /usr/local and runs from the $PATH environment. Running Wineskin containers is as simple as exporting WINEPREFIX=/Users/user/Applications/Wineskin/TheBundle.app/Contents/Resources and running wine on the binary. If it's something like Steam that starts on boot, it should be sufficient to run:
wineboot 2>&1 > /dev/null &
From a Terminal.