Japan
Japan isn't so much a symbol as it is a magnifying glass that blows up the communication barricades around Bob and Charlotte. Even day and night are switched around because of the 12+ hour time difference from the states, and that adds to their sense of disorientation.
The country's culture is alien to both of them, but they react to it differently. Charlotte studies things like the recent college grad that she is. She loiters in the arcade, watching people play video games with guitar and dance pad peripherals she's never seen before. She seeks out temples and tries her hand at ikebana.
Bob, on the other hand, often resorts to jokes, some of them arguably offensive, when he clashes with Japanese culture. Check out the "joke" he makes at the restaurant about Charlotte's broken toe:
BOB: Well, you either go to a doctor, or you leave it here… See, they love black toe over in this country… Gotta be. You know, this country? Somebody's gotta prefer black toe. "Ah, brack toe." We should probably hang around until someone orders it?
Hilaaaaarious, right? Japanese speakers of English often replace Ls with Rs and they eat weird (to us) stuff. Isn't that just the funniest?
Yeah, not really. Bob frequently dabbles in Asian stereotypes for "humor" which is (A) a bummer, and (B) his way of dealing with a foreign world that's just as scary as it is exciting. We all have that friend who makes lame jokes when they get nervous. Who knows? Maybe you are that friend. No judgment.
On top of the Japanese culture clash, there's the hefty language barrier. In Japan, Bob and Charlotte literally don't speak the language. This parallels the fact that, even at home in America, they don't really speak the language. Roughly 95% of Bob and Lydia's phone conversations are about remodeling their home, for example, and, when it comes to the other 5%, they aren't on the same page at all. Check it out:
LYDIA: Look, your burgundy carpet isn’t in stock. It's gonna take 12 weeks. Did you like any of the other colors?
BOB: Whatever you like. I'm completely lost.
LYDIA: It's just carpet.
BOB: That's not what I'm talking about.
LYDIA: What are you talking about?
BOB: I don’t know. I just want to get healthy. I want to take better care of myself. I would like to start eating healthier. I don't want all that pasta. I would like to start eating like Japanese food.
LYDIA: Well, why don’t you just stay there, and you can have it every day.
Lydia doesn't understand where any of this is coming from because she has no context for it, and Bob doesn't understand why Lydia's hostile to him because he has no concept of what running their home is like.
Bob navigates Tokyo the same way; he's quick to jump to a joke, his natural defense, because he doesn't understand where anybody's coming from, and they don't understand him either. Because of these culture and communication obstacles, there's a lot that gets literally "lost in translation" for Bob and Charlotte during their stay in Japan.
Japan represents all the alienation and misapprehension that drives both characters inward first, and then to each other.