God. He wants them to find this cup...[Ed. See "Monty Python and the Holy Grail if you cant figure this out] A new lake/chasm blocks the road... Demons/Dragons have set up shop on the road. Steady supply of food.
Of course, more sensibly: Many small towns, villages and homesteads, with associated townsfolk. Village rumors and scandals can be a great add to a campaign. Gives and sense of the real world existing. Not just BIG magic, monsters, cities. Normal people are around too. They shouldn't just be Background (or god forbid, cannon fodder).
And if you really want to confuse your players
Another city. Unmapped. Perhaps illusory, perhaps it only overlaps the world once every hundred years or so. Or the players just get mislaid by bandits who altered the road to lead to a previously abandoned city, lost to time (great for BG). Imagine their surprise as they come to what they assume is the proper city and find it completely abandoned (save for traps from the bandits).