The size difference between Vince Vaughn and Reese Witherspoon isn’t the only thing keeping them apart in “Four Christmases.”

His signature rat-a-tat overconfidence and her pleasing girl-next-door perkiness turns out to be an awkward mix. Individually likable, Vaughn and Witherspoon never really seem to mesh as a couple.

That’s a problem, since we’re meant to root for them to stick together. It doesn’t help that they’re saddled with hackneyed holiday gags: wacky relatives making inappropriate remarks, decorations that cause severe bodily harm, obnoxious kids, uncomfortable gift exchanges.

And “Four Christmases” began with some promise, too.

Vaughn’s Brad and Witherspoon’s Kate are a happily unmarried couple sharing a coolly industrial-chic house in San Francisco. They like to keep things lively by role-playing at bars, as they do in the film’s amusingly naughty opening, and they lie to their families about doing charity work each year to avoid seeing them during the holidays.

So far, so good.

Then, when they’re caught live on the news getting stuck at the airport on the way to Fiji, they get roped into seeing both sets of parents, who are divorced, hence Brad and Kate’s own apprehension about walking down the aisle. And so they must celebrate — let’s all say it together — four Christmases.

The visiting begins in painfully broad fashion with Brad’s family, all white-trash stereotypes led by Robert Duvall. (Vaughn’s longtime friend and collaborator, a freakishly muscular Jon Favreau, and Tim McGraw play his ultimate-fighter brothers.) The noisy joylessness of this segment sets the tone for the whole movie, and it makes you wonder how it’s possible that it took four screenwriters to come up with this stuff.

Next, they’re off to see Kate’s mom (Mary Steenburgen), who’s found the Lord now that she’s involved with a rock-star preacher (Dwight Yoakam, underused). Kristin Chenoweth plays her smugly married-with-children older sister in a perfect bit of casting; it’s amazing she and Witherspoon never shared the screen before. It’s also amazing that, after dating for three years, neither Kate nor Brad has met the other’s family until now.

The third stop is at Brad’s mom’s house, and speaking of a complete waste of talent, Sissy Spacek gets to do little but beam benignly as a rich Marin County hippie. Finally, they end up at the upscale home of Kate’s father (Jon Voight), but by then the couple’s relationship is hanging by a thread. After attempting to offend us in every imaginable way, “Four Christmases” has the chutzpah to try tugging at our hearts, with a half-baked conflict about Kate’s sudden desire to get married and start a family — as if any of their hideous visits would inspire such an instinct.

Vaughn makes the movie tolerable here and there, but this kind of slapsticky physical comedy doesn’t suit Witherspoon at all. Director Seth Gordon, making his feature debut following the critically acclaimed documentary “The King of Kong: A Fistful of Quarters,” fails to make optimal use of the qualities that make this bright actress shine.

It isn’t funny when a baby spits up on her the first time; then again, it would be a lame joke regardless of who was covered in yack.