Several years ago, a "friend" of mine sat me down to watch the first fifteen minutes of one of the One Piece movies. I think it was called Strong World? He assured me it would be super awesome and also would make sense without any context. As it turned out, neither of these things were true, but it was very colorful and I think featured some islands? Anyway, prior to today, that was the extent of my experience with One Piece.
Oh, other than that one really good AMV set to Come Sail Away by Styx that I saw at an anime convention when I was like fourteen. That was a sweet AMV.
The first episode of One Piece establishes a few important things about the setting. As someone coming into the show without knowing anything about it, this is useful. First of all, we know that this is a world with baseball. Therefore, this anime is about baseball. That might not be immediately apparent to the casual viewer, but we begin with sailors attempting to score a homerun against a mysterious floating barrel, but eventually they strike out, tragically.
We also learn a number of things about our putative protagonist, "Monkey D. Luffy." For one thing, his name is Monkey. Why? Is he a Monkey? If so, does he have any relation to the Monkey-tailed protagonist of Dragon Ball? Is this secretly a prequel to Dragon Ball? Is Monkey actually Goku's father? Is the One Piece actually just the Dragon Balls?
Probably. Let's go with probably.
Monkey D. Luffy is not intelligent. He seems to have a fundamental lack of understanding as to what a "pirate" is and what a "pirate" does. This raises additional questions about the setting--if this is a Golden Era for Pirates, has the definition of piracy fundamentally changed? Or is Monkey just not very smart? The fact that on a quest for food, his first step is to leave the kitchen seems to imply that Monkey's intelligence may not be generally up to snuff.
Shortly after knocking a stranger unconscious, Monkey declares that he is going to get a boat (his previous one having apparently been lost with all hands1 in a whirlpool). He will also need a crew for his boat--presumably in order for them to compete in the upcoming baseball tournament. This is a reasonable quest, as a full baseball team takes quite a few crew members! I wish Monkey D. Luffy the best of luck on his ongoing endeavor to win a baseball game. I hope it doesn't take him too many episodes.
In conclusion, One Piece is probably about baseball.