If you've ever been annoyed by this one:
You may find the following Run Script interesting which is simply added as a Build Phase.
This will kill your currently running iPhone Simulator instance, then sleep for two seconds to prevent Xcode from nagging you (see first screenshot) and return 0 to ensure we won't exit with a statuscode of 1 in case no simulator is currently running.
For easy copy and paste:
killall "iPhone Simulator"; sleep 2; exit 0;
That's it folks!