Since we're on the subject, I would proffer that Abigail Adams would be the first choice considering she was an original lady from the founding fathers' time. Furthermore, her letters between her and her husband are focal points in American literature classes in most colleges. If you read them and appreciate the era and what they were going through to create a new country it is quite revolutionary and meaningful thus deserving of her portrait on US currency if it actually was honest money instead of debt money. In which case, I have no problem w/ Moochelle Obama being on the next piece of currency.
Just a short recap of AA's bio:
Adams's life is one of the most documented of the first ladies: she is remembered for the many letters she wrote to her husband while he stayed in Philadelphia, Pennsylvania, during the Continental Congresses. John frequently sought the advice of Abigail on many matters, and their letters are filled with intellectual discussions on government and politics. The letters serve as eyewitness accounts of the American Revolutionary War home front.
If you can find it there was a show about the Adams's on one of the premium cable channels not long ago. Paul Giamatti played John Adams. They were a remarkable couple that made large sacrifices for the good of the country. We could use political families like that today for sure.