We report the findings of a detailed assessment of various options for computational two-fluid RANS simulations of an aerated agitated 2-L bioreactor equipped with a single baffle and several dip tubes. The simulations were carried out by using the commercial flow solver ANSYS/Fluent. Our focus was on (1) the outlet condition at the liquid's surface (i.e., including an air head space in the simulation yes or no); (2) the choice between the steady-state Multiple Reference Frames (MRF) approach for modelling the impeller rotation and the dynamic Sliding Mesh (SM) option; (3) the choice between two computational meshes (mosaic or polyhedral); and (4) the effect of using either the realizable k-ε model or the SST k-ω model for dealing with the turbulence in combination with different values for the fixed bubble size (either 1.8 or 2.8 mm). The final conclusion is that the SM impeller model in combination with a polyhedral computational mesh and the SST k-ω turbulence model is to be preferred. All simulations suffer from the occurrence of spurious velocities larger than the impeller tip velocity.