Generic answer: it depends on your fuel -- if you are all electric, a forced-air mini split will be better than electric resistance baseboard, which is the least efficient system you can get.
Best advice: get an energy audit to determine the true reason why the main floor is cold. Are there insulation issues, air sealing issues, HVAC duct issues? Once you pinpoint the cause, you can get a customized solution.
If you are serious about fixing your house, and making it more efficient, spend $400 or $500 on an energy audit. It'll save you thousands of dollars by not assuming a solution and installing the wrong thing. A list of independent auditors in the DC area can be found at www.mdhomeperformance.org.
For more information:
GreenHomeGuide's Find a Pro directory is another resource that can help you locate a qualified home energy auditor.