One difference of course is the syntax. But I'm guessing the idea is eventually quantum computers will be able run Q#, whereas now it uses simulations. Will code written in Python with the qSharp library also be able to do this?
There are several separate questions entangled here.
Using Q# with Python as the host language is similar to using Q# with C# or another classical host language: it allows you to run Q# code and do necessary classical processing (for example, preparing the data or analyze the results). The Q# code invoked from the classical host language has to be written somewhere - it will be either the library code or the code you wrote yourself.
Learning Q# language itself allows you to implement any algorithm you want; without doing that, you'll be limited to using algorithms implemented by somebody else. That's certainly possible.
Running the program on quantum hardware vs in simulation is completely independent from the way you run it (from Python, C# or in standalone mode) - it's a matter of configuring the right target machine.