In a two story house is there any reason not to put the only heating and a/c unit on the second floor?

Thank you

There are concerns of vibration of the AC unit, and of course the heat being too close to combustibles. But units have been installed on upper floors many times, as long as the two issues I mention are considered.

Proper venting of flue exhaust and fresh air for combustion are also concerns that must be addressed.

Best to check with local codes to be sure it is installed properly for comfort and safety.