We explore the nature of systematic errors that can arise in measurement of black hole masses from singleepoch (SE) spectra of active galactic nuclei (AGNs) by utilizing the many epochs available for NGC 5548 and PG1229+204 from reverberation mapping (RM) databases. In particular, we examine systematics due to AGN variability, contamination due to constant spectral components (i.e., narrow lines and host galaxy flux), data quality (i.e., signal-to-noise ratio (S/N)), and blending of spectral features. We investigate the effect that each of these systematics has on the precision and accuracy of SE masses calculated from two commonly used line width measures by comparing these results to recent RM studies. We calculate masses by characterizing the broad Hβ emission line by both the full width at half maximum and the line dispersion, and demonstrate the importance of removing narrow emission-line components and host starlight. We find that the reliability of line width measurements rapidly decreases for S/N lower than ∼ 10-20 (per pixel), and that fitting the line profiles instead of direct measurement of the data does not mitigate this problem but can, in fact, introduce systematic errors. We also conclude that a full spectral decomposition to deblend the AGN and galaxy spectral features is unnecessary, except to judge the contribution of the host galaxy to the luminosity and to deblend any emission lines that may inhibit accurate line width measurements. Finally, we present an error budget which summarizes the minimum observable uncertainties as well as the amount of additional scatter and/or systematic offset that can be expected from the individual sources of error investigated. In particular, we find that the minimum observable uncertainty in SE mass estimates due to variability is 0.1 dex for high S/N ( 20 pixel −1 ) spectra.