The reduction of virgin bitumen added to asphalt mixtures containing Reclaimed Asphalt Pavement (RAP) is based on the typical assumption that all the aged binder function in the same way as the virgin binder. However, recent studies conducted by the authors for a specific case show that a blend or mobilization of RAP binder are negligible. The aged bitumen becomes softer acting as glue facilitating cluster formation between small-size RAP particles. The reduction of small-size particles causes changes in the target grading curve and in the voids-fill, affecting the compactability of RAP mixtures. Therefore the target grading curve of RAP mixtures needs to be readjusted, using different proportions of virgin aggregates and taking into account the cluster phenomenon. The objective of this paper is to develop a new mix design approach for RAP mixtures, taking into account the cluster phenomenon and the contribution of the aged bitumen in the compactability. The virgin aggregates, filler and RAP are investigated and individually included in the calculation. 3D images of the virgin aggregates allowed the determination of new surface area factors; the concept of critical filler concentration led to the definition of the minimum bitumen quantity required to maintain the mastic in a diluted state and fill the voids. A RAP clustering model was introduced to predict the agglomeration of small-size RAP particles. The readjustment of the target grading curve was analytically calculated, allowing the correct estimation of the amount of virgin bitumen to be added to asphalt mixtures. Finally, a first verification of the entire process was carried out performing laboratory tests. These promising results enable the challenge of a new mix design optimization for HMA with high RAP content to be addressed.