The rotating reference frame is usually preferable over an inertial reference frame when analyzing three-body motion. Two main reasons for this:
- The motion is determined by the two primary bodies, so it makes sense to use these to define the reference system
- The typical three-body dynamics for which you would use such a reference system, such as Libration point orbits arise from the equations of motion in the rotating reference frame. The Libration points are only defined in their classical way in the circular restricted three-body problem.
This of course doesn't mean that Inertial can't be used. You could recreate the same orbit in an inertial reference frame, the main problem is that the dynamics will not be recognizable as for example a libration point orbit. A Sun-Earth L2 Halo orbit will look like a plain heliocentric orbit if you look at it in an inertial sun-centered reference frame.
As a final note, libration points and their respective orbits are defined in the Circular Restricted Three-Body Problem. The real-life situation is as you might expect radically different from the CRTBP. You have eccentric orbits, leading to both a change in the distance between the primaries as a non-uniform rotation rate. On top of this you have all kinds of perturbations from other solar-sytem bodies, solar radiation pressure, non-uniform gravity,...
For recreation of CRTBP dynamics in the real-life situation, something interesting to look at is a Rotopulsating Reference frame. The reference frame is centered at the barycentre of the two primary bodies and rotates along with the line connecting them both. On top of this, the distance is scaled so that the distance between the two primaries is always equal to 1. This translation of the CRTBP reference frame to a real solar system model is unfortunately highly non-newtonian because of its non-uniform rate of rotation (Roto-) and changing definition of distance (Pulsating).
This makes the derivation of the equations of motion quite the challenge but if you are interested, check out this thesis for a detailed explanation and derivation.