I picked up Inventor Nastran last year because its part of our corporate license package and was getting little use. I taught myself based on my knowledge of Creo Simulate (and years ago, Ansys Designspace connected to SolidEdge). With that background it was straightforward.
Big picture: I work for a company that was bought by a larger competitor. I spent 15 years using Creo and Creo Simulate. Now the corporate mandate is Inventor and Ansys for simulations. However, Ansys was a big jump for various reasons so I explored Inventor Nastran before Ansys.
The user needs to understand finite element analysis. None of these softwares are acceptable for use by users who can run CAD software but have not had robust solid mechanics training. All of them require some sense of 'good' and 'bad' results as well as how to construct different variations of the model to establish proper model behavior and convergence. Even Creo Simulate, with its excellent convergence algorithms, sometimes does not give a well-converged solution.
The real difference is that Inventor Nastran and Creo Simulate are parametrically connected to the geometry. When your design needs to evolve based on the simulation results, Inventor Nastran and Creo Simulate are the right tool. When there will be no evolution (only pass/fail) or highly advanced simulation methods are required, you need to use a standalone FEA tool. Inventor Nastran and Creo Simulate do limited nonlinear studies.