When the boundary layer separates, its remnants form a shear layer and the presence of a separated flow region between the shear layer and surface modifies the outside potential flow and pressure field. In the case of airfoils, the pressure field modification results in an increase in pressure drag, and if severe enough will also result in  stall and loss of lift, all of which are undesirable. For internal flows, flow separation produces an increase in the flow losses, and stall-type phenomena such as compressor surge, both undesirable phenomena.
Another effect of boundary layer separation is regular shedding vortices, known as a Kármán vortex street. Vortices shed from the bluff downstream surface of a structure at a frequency depending on the speed of the flow. Vortex shedding produces an alternating force which can lead to vibrations in the structure. If the shedding frequency coincides with a resonance frequency of the structure, it can cause structural failure. These vibrations could be established and reflected at different frequencies based on their origin in adjacent solid or fluid bodies and could either damp or amplify the resonance.