It's important to be in the habit of listening in different formats and contexts.
I've got things set up so I'm just a button press away from choosing between my monitors, some fairly nice hi-fi speakers, a pair of pretty nasty Dell computer speakers, and a headphone out with earbuds. And I've got Panipulator in the master bus of my standard template. The monitors are for doing the actual work, and the other options are for various verifications and checks.
I also routinely upload works in progress to soundcloud so I can listen to them on headphones while I'm walking down the street. That's a great test. For one thing, soundcloud streaming quality is pretty terrible; I think 128k mp3, more or less. And listening to 128k on earbuds walking down a busy street; well, you've got yourself a mainstream use case right there. If your mix holds up in that situation, then YOU DA MAN.