What frame of reference should I use for my Simulink simulation of the F/A-18 Hornet?
It's very prudent of you to be concerned about the axis frames in which different forces/motions are defined. It's a common mistake to ignore the fact that aerodynamic coefficients are normally defined in wind axes.

The standard approach is to calculate Equations of Motions in the body frame; this is how they are usually defined. For this, you'll indeed need a wind-to-body matrix (DCM). This is a simple matrix because it involves only two angles (beta and alpha), and these angles are normally small to be concerned about gimbal lock (the model is probably not defined where they are not small). Then you


Calculate the forces/moments that are defined in wind axes and rotate them to body.
Likewise, calculate forces and other things that are defined in the ground frame, such as gravity and wind per se, and rotate them to body. (It makes sense to use quaternions for that rather than DCM, but this is another matter).
Finally, you'll have forces that are defined directly in the body frame, such as thrust.


Now you can integrate EoM with all the data available in the body frame.

Regarding p, q, r (and such) used in calculation of the aerodynamic forces, these are usually body angular velocities that you can take directly from your EoM. However, you should double check if the aerodynamic model requires something else; this should be explicitly defined. Note that if you do need to rotate angular velocities, you can't use the same DCM but need to use the matrix that preserves the total angular momentum.