In a perfect scenario in theory it is a little more expensive for two, but in practice and actual use should be about the same or cheaper. Each unit has approximately half the load with typically an upper unit having the larger half since cool air is heavier than hot air and flows down. With each equally efficient you would say it costs the same. But a larger unit can be made more efficient and the on-off cycle uses a startup extra charge. Two units are often side by side so are warmer next to each other by exhaust. You also have a higher chance of extra service calls. Most of the variation of the total is going to be about insulation in losing cold air from inside and heat coming in plus the climate variation.
However, the reason for the two units is key. People like a stable temperature, or be able to control and may allow upper floors as less used to get warmer in certain parts of the day, or even reversed if upper floors are for sleeping and a cooler level is desired at night. For a single unit to be constant temperature throughout 4 levels, it would take a control of air at each room intake and some kind of air flow set up through the home. Often, to get upstairs cooler the downstairs gets cold. Efficiency is lost. It can also go the other way with frequent door opening on a lower floor or cooking and the refrigerator all putting more work on the lower unit. When considering load splitting, climate and construction, and human behavior, two units are better than one larger one.
With new AC efficiencies, it is mostly in climate and insulation. Another advantage of two units is that if one goes down, it does not get unbearably hot inside in some climates like Las Vegas where I live. When the AC unit fails for need of repair, it truly is an emergency call. With two units, you can schedule at a convenient time and even last a day or two without a lot of issue.