Before you comment, remember that I said ‘if’, not that it should be.
Ninjas instead of thieves.
Angels and demons, vampires, witches, dragons, unicorns, fairies and pirates would all be ‘core’ classes or races. [note: this was written before tieflings became a core race]
Talking animals would be much more prominent. There would probably be several species: wise owls, loyal dogs, arrogant cats, cunning foxes…
The setting wouldn’t necessarily be entirely cut off from the real world. Maybe there’s a fantasy world hidden in the real world (Buffy, World of Darkness), or maybe some people from the real world are transported to the fantasy world (Narnia).
No clerics. There might be characters who heal, there might be characters who smite the undead, and there might be priests. But they wouldn’t necessarily be the same group of people.
Luck and Courage would likely be important stats of some kind.
A clear and detailed taxonomy of monsters probably wouldn’t exist. For example goblins, hobgoblins and orcs might be the same species (or at least the PCs and most humans might use the terms interchangably).
Zombies would be a prominent enemy. They would be the ghoul-like, virus-carrying zombies of Day of the Dead rather than the zombies of folklore.