Profound and important truths are often hidden in sayings so common and familiar that we don't hear them anymore. Perhaps the most important truth that can be boiled down to a platitude is this: "God grant me the serenity to accept the things I cannot change, the courage to change the things I can, and the wisdom to know the difference."
Every unhappy person I've ever known could be neatly divvied up into those three categories. People who couldn't accept what they couldn't change: who would gnash their teeth and wear themselves out being outraged at injustices, or burn their spirits down trying to fix things (or other people) that were beyond their reach. People who lacked the courage to change what they could: who sat around letting life slip by without setting goals and working towards them, who coasted on the charity of others, who were mired in entitlement or dependency. Or people who gave up on some things they shouldn't, but strained long past the point of sensible surrender on things they couldn't do.
And by the process of elimination, every happy person I've ever known was someone who took responsibility for themselves and their lives, who figured out what they wanted and then worked towards it all the time, but who didn't aim so much too high that they never got moving, and didn't waste their spirit on crusades they could never achieve. Who were content to do their part, no more and no less, in making both their own lives and the world better.
Too bad the saying is so mired in kitschy framed plaques to be appreciated as the single fact most unhappy people most need to absorb to make their lives better.