In one aspect, a system and method allow for various pairs of candidate gear ratios and engine speeds to be identified for achieving a desired ground speed of a work vehicle. The individual operating efficiency of the vehicle's fan and/or alternator may then be analyzed for each pair of transmission/engine settings to estimate the associated parasitic power loss(es) for such component(s). Based on the parasitic power loss(es) determined for each transmission/engine setting, a net engine power or torque requirement can be calculated and used as an input for determining the fuel efficiency of the work vehicle at each candidate setting. The gear ratio and corresponding engine speed of the candidate setting associated with the lowest fuel consumption may then be set as the target or desired transmission/engine setting for maintaining the work vehicle at the desired ground speed.