Vehicles will despawn, though I'm not sure what it's based on. Dunno if it's total time on the road, or if it's based on being stuck in a jam for too long, or what.

In any case, a vehicle that despawns is a cancelled trip. A commercial building won't receive its goods. A worker won't get to work. If your city's traffic is bad, a significant number of trips won't complete, and your commercial districts will abandon due to lack of workers or lack of goods, industries will abandon due to lack of buyers or lack of raw materials, and residential will abandon due to unemployment.

Despawning affects service vehicles too, so if they're frequently being despawned, garbage piles up, people get sick and die, crime goes up, etc.

There are mods that will disable despawning. But in a large city, this will likely make your roads turn into gridlock. Once this happens, nobody reaches their destination, and your city quickly goes to shit.