GOWER'S VOICE: I owe everything to George Bailey. Help him, dear Father.
MARTINI'S VOICE: Joseph, Jesus, and Mary. Help my friend Mr. Bailey.
MA BAILEY'S VOICE: Help my son George tonight.
BERT'S VOICE: He never thinks about himself, God; that's why he's in trouble.
ERNIE'S VOICE: George is a good guy. Give him a break, God.
MARY'S VOICE: I love him, dear Lord. Watch over him tonight.
JANIE'S VOICE: Please, God. Something's the matter with Daddy.
ZUZU'S VOICE: Please bring Daddy back.
We hear these prayers from family and friends at the very beginning of the movie. These very first lines tell us what kind of good friend George is. Heaven is practically flooded with appeals to help him.
GEORGE (exasperated): Seen your wife? I've been to your house a hundred times.
ERNIE: Look, bud, what's the idea? I live in a shack in Potter's Field, and my wife ran away three years ago and took the kid ... and I ain't never seen you before in my life.
George is shocked that Ernie doesn't recognize him in the alternate universe. His emotional reaction to Ernie's rejection gives him a taste of what life would be like without friends.
CLARENCE: Strange, isn't it? Each man's life touches so many other lives. When he isn't around, he leaves an awful hole, doesn't he?
George doesn't think of himself as important, but he does have tons of friends. That's why Clarence can use the strategy that he does; George cares about the people he'd leave behind.
HARRY: Good idea, Ernie. A toast ... to my big brother, George. The richest man in town!
Jimmy Stewart remembers Frank Capra saying after the film wrapped, "No man is poor who has one friend. Three friends, and you're filthy rich!" (Source)
CLARENCE: Dear George, remember, no man is a failure who has friends. Thanks for the wings. Love, Clarence.
In case we didn't get it before, Clarence drives home the movie's theme.