I am building a new house. I am considering installing two 40 gallon water heaters rather than one 80 gallon water heater. My thought is that I could turn one the 40 gallon heaters off as there are only two of us most of the time. Then we could turn on the other when we have guest. Is there a savings with the two heaters that would pay off the additional cost of two heaters in a reasonable time?

Guess I am missing how you would plumb two heaters,

If you are looking for Cost efficiency and the bath for guests is Rarely used a Inline Heater in this bath would be the best as it would only be used when the guest uses this bath. If there are only two of you Inline Heaters are Very Efficient and would provide Plenty of Hot Water for all your Needs. I have Inline on Three Levels of our home, to Each baths Hot water Piping. The Main Advantage is there is no Heating Element on Unless the Water is Flowing thus your not heating water and keeping it at temperature while nobody is using it. But if you Want traditional Tank Heaters if the home is Large Two Systems with Cross connect is Good Also but far less Efficient.