Climatic conditions determine which retrofit strategy can result in a satisfactory improvement of a building's thermal performance. This study systematically investigates alternative retrofit actions, as standalone and in combination, and assesses their energy performance. The retrofit actions include i) insulation on the external walls, ii) the incorporation of phase change material (PCM) on the roof and the increase of the building thermal inertia, iii) a mechanical ventilation system with a summer period operation, and iv) a cool roof coating. The energy analysis concerns a typical two-story family building and the four climatic categories of Greece and is conducted with the INTEMA.building tool, a dynamic energy analysis software developed in Modelica language. The importance of the present study is that it serves as a guideline for the selection of the energetically optimum single retrofit or multiple-retrofit strategy regarding a building's location climatic data, and provides calculations concerning the annual heating and cooling loads, and the corresponding heat pump electricity consumption. The retrofit actions of external wall insulation and PCM roof addition are characterized as more effective in reducing a building's heating energy loads, while the mechanical ventilation system and cool roof coating are more effective in reducing a building's cooling loads. The quadruple retrofit strategy results in the maximum electricity savings for Heraklion (28.01%), Athens (21.15%), and Thessaloniki (16.54%), while the triple retrofit strategy which does not include the cool roof coating, results in the maximum electricity savings for Kastoria (10.79%). Lastly, an economic analysis of the energetically optimum renovation strategies is conducted.