Alexander Hamilton and John Adams led the federalists(D).
Answer:
Disagreements over federal laws, goverment and matters, are the most likely cause for secession in Modern America.
For example, if the federal government passes a law that taxes certain economic activities very high, and these activities are very important for a particular state, that particular state could start a secessio process, although such process would not be likely to succeed.
Another possibility is if a state inhabitants simply become nationalist and start separatist movements.
