Using the system Python for scripts that only depend on the standard library should be pretty safe. As soon as I need any third-party dependency I create a virtual environment.

Edit: Although if startup performance is important, using a virtual environment might be a good idea even for simple scripts. Running a "hello world" program using the system Python takes twice as long on my system as running it with "python -S" (i.e. ignoring site packages) or from a fresh virtual env.