For 50-50/double up/headsup games, you're looking to maximize your mean projected points.
For games with different payout structures (like a triple up/quadruple up), a lineup with the highest mean projected points is often times not the optimal play. In those formats, you want to seek higher variance lineup combinations (Selecting teammates/linemantes is the easiest way to do this...QB/WR combos in football). The reason for this simply is that payoffs are not symmetrical. A really bad result pays the same as a league average result ($0). You're interested in maximizing the probability that a high variance event will happen for your team, even if it degrades the expected mean points of your team for a given night.