It does matter if people aboard, there are more rules and procedures. You need a vessel with safeties that can allow them to eject safely if there's an anomaly.

Of course it's more challenging.

And it does matter if there's more fuel, you have to have valves and pipes that won't freeze after lengthy contact with cryogenic fuel. And you need larger pressure vessels, which scale in volume differently from surface area. It's not at all the same whether you move one ton or a hundred.