Recent theoretical studies have shown that charge transport in high-mobility organic semiconductors is limited by low-frequency vibrations because of strong non-local electron-phonon interaction. Here we investigate two high-electron-mobility organic semiconductors with similar molecular structures but considerably different crystal packings, TCNQ and F2-TCNQ, and reveal the relationship between the experimental low-frequency Raman spectra and the calculated contributions of various vibrational modes to the electron-phonon interaction. We suggest that the combination of Raman spectroscopy with solid-state DFT is a powerful tool for probing electron-phonon interaction and focused search for high-mobility organic semiconductors.