In the last few decades, a series of earthquakes were recorded which pointed out several deficiencies regarding the ductile seismic response of MR RC frame structures. Thus, the research problem centres around the failure mechanisms registered by the structures, which differ from the general notions of seismic response commonly found in current design standards and norms regarding seismic actions. In these conditions, in the present paper—by using comparative methods—the analytical validation of the solution of plastic hinge concentration and seismic energy dissipation in the marginal beam areas is proposed. Therefore, the RC beam sections were reduced (weakened) in the marginal areas which exhibit a plastic deformation potential, as well as in the corner areas of concrete slabs with vertical rectangular holes. The significant outcomes of this research imply the partial “guiding” of plastic hinges in the zones adjacent to beam ends. Furthermore, a reduction of both the negative effects of horizontal rigidization of the beams and the cracking and plastic deformation effects of beam-column frame joints was observed. With these technical implications, a complex mechanism of plastic deformation of MR RC frame models is registered in which all lateral elements (including RC columns) participate in the dissipation of seismic energy, without the occurrence of the “weak storey” mechanism for any of the analytical RC frame models. Furthermore, it is possible to observe the partial formation of the global plastic mechanism “Strong Columns—Weak Beams” (SCWB) for some of the structural models. Finally, the analytically studied innovative element regarding the improvement of the seismic response of pure MR RC frame structures is successfully validated.