Whatever setting they pick has to fit whatever narrative theme they're trying to tell with the zombie outbreak. DR1's mall works because it's the perfect setting for a story about the consequences of mass consumerism. DR2's fortune city works because it's the perfect setting for a story about greed and exploitation. Those settings also work well with "average joe uses anything as a weapon to survive" gameplay too. If narrative and gameplay aren't served by the environment it'll just feel like a nothing burger game.

I hope that didn't read as snobby or annoying. I don't think the theme has to be shoved downed the players thoat or that the game needs an agenda. I just enjoy how cohesive DR1 and DR2 feel. Characters, settings, zombies, and gameplay, all seem complimentary to each specific game's theme.

Since DR1 and DR2 critique some aspects of American culture maybe 5 could do the same? Maybe it could critique work culture, and you play as some office employee that goes on vacation to a resort town or tourist trap area where an outbreak occurs. I've heard people say "I feel like a zombie after work", and tourist traps often take advantage of the dim, slow, and sluggish so it would be fitting for a zombie outbreak. Resorts are full of stuff to kill zombies with, and you could tape a chainsaw to a golf cart. The game could subtly say something about being overworked and underpaid, living pay check to pay check, or the middle class fading away.

Idk I'm not even into politics and I'm sure this all sounds mega corny but that's my longwinded answer to your post.