I travel a lot throughout the US, and sometimes the changes are obvious while other times I can be driving and not entirely sure which state I'm in just from looking around on the highway. As others have said while driving on a major highway a clue can be a huge store full of items like fireworks just across the border from a state they aren't legal in.
The geography and environment can certainly be a big clue. Driving through West Virginia there are tunnels through large mountains, Pennsylvania around the Pittsburgh area has steel bridges, Louisiana has highways raised up from the muck, there are mountains that the highways wind around in North Carolina that give way to pretty flat highways as you go south. Kentucky has long depressing stretches of straight boring road. I've noticed even traffic patterns can say things as Georgia highways always have a higher number of semitrucks than anywhere else for example. Nevada is flat and open but as you go into Utah it gets windy and rocky, and cell signal usually goes out for a bit.
Staying in different states I notice alcohol sales rules are different. In some states you basically don't see any alcohol outside of designated stores for it including no beer at gas stations, in other states you see beer for sale widely but hard liquor only at designated stores, and in other states hard liquor at WalMart is perfectly normal.
I've found on the whole that people are actually nicer than average in Utah. While coffee shops exist I have noticed in offices there is often a lack of a central coffee machine.
Louisiana everyone I deal with from there has a tendency to be much more relaxed than average about showing up exactly on time for things. Louisiana itself also has a cultural divide between the northern part which is more generic US south, and the southern part which has the more creole and tourist heavy atmosphere.
I honestly don't mind Ohio. I know it's an internet meme to hate it, but aside from their obsession with dumping chili on unrelated foods it's decent. Has a strong blue collar streak kind of like Pennsylvania culture.
Texas has a big cowboy influence and they don't let you not know it. The roads tend to big big and wide which is great, except the freeways especially in Dallas can become confusing multilevel nightmares.
California has lots of Spanish signs, lots of first generation Mexicans who bring culture with them. Lots of for example Mexican super markets. Californians have a culture of going FAST on freeways if there isn't gridlock traffic, in some cases going 100mph just barely keeps you up with traffic.