The behavior of structures under earthquake excitations is significantly affected by various ground motion characteristics, including energy distribution, frequency, amplitude, fault location, and the duration of intense shaking. A comprehensive understanding of the complex connection between these earthquake parameters and the response of structures is essential for improving design strategies to enhance earthquake resilience. This study examined how earthquake amplitude, significant shaking duration, spectral displacement, and energy content affect the seismic performance of mid-rise reinforced concrete frame structures, using a representative 6-story model, commonly found in emerging economies such as India, Nepal, and Pakistan. The study employed nonlinear time-history analysis with a set of 20 short-duration earthquake events to evaluate the influence of Housner intensity (Ih), peak ground motion amplitudes, significant shaking duration, and spectral displacement (Sd) on structural response. Results revealed that peak ground velocity was the most reliable amplitude-based parameter, while significant shaking duration weakly correlated with structural roof displacement (Δroof). Ih, representing total energy, was identified as a key parameter highly correlated with Δroof. Moreover, at lower peak ground acceleration levels, larger Δroof occurred due to higher Sd at the structure’s fundamental period. The findings highlight the significance of both the time-dependent and frequency-dependent properties in assessing structural performance and enhancing seismic design considerations.