In densely populated urban areas, reinforced concrete residential buildings with an open first floor and closed upper floors are preferred to meet user demands, resulting in significant vertical stiffness irregularities. These vertical stiffness irregularities promote the development of a soft-story mechanism, leading to concentrated damage on the first floor during seismic events. To mitigate seismic damage caused by the soft-story mechanism, stiffness-based retrofit strategies are favored, and it is crucial to determine an economically optimal level of retrofitting. This study aims to establish optimal seismic retrofit strategies by evaluating the seismic losses of buildings before and after stiffness-based retrofitting. An equivalent single-degree-of-freedom model is established to describe the seismic response of a multi-degree-of-freedom model, allowing for seismic demand analysis. By convolving the seismic loss function with the hazard curve, the annual expected loss (EAL) of the building is calculated to assess the economic losses. The results show that stiffness-based retrofitting increases first-story lateral stiffness by 20-40%, enhancing structural seismic performance, but also results in a rise in EAL compared to the as-built state, indicating lower cost-effectiveness from an economic perspective. The research concludes that retrofit options that increase first-story lateral stiffness by at least 60% are more appropriate for reducing financial losses.