1. The creation and acquisition of territories
2. The wars with foreign nations
3. The role of the Federal Government and revenues
4. Economic control and power
5. The power of religion and education
6. The Indian Wars and treaties
Any of these could had brought about secession since secession had always been believed to be a fundemental right of the soveriegn States, and which several States reaffirmed in the 1798 when the thought of secession was very real when the Federal Government pass the Sedition Acts. This prompted several states to declare the Federal Government had overstepped its power.
"To address the constitutionality of the measures, Thomas Jefferson and James Madison sought to unseat the Federalists, appealing to the people to remedy the constitutional violation, and drafted the Kentucky and Virginia Resolutions, which called on the states to nullify the federal legislation. The Kentucky and Virginia Resolutions reflect the Compact Theory, which holds that the United States is made up of a voluntary union of states that agree to cede some of their authority in order to join the union, but that the states do not, ultimately, surrender their sovereign rights. Therefore, under the Compact Theory, states can determine if the federal government has violated its agreements, including the Constitution, and nullify such violations or even withdraw from the union. Variations of this theory were also argued at the Hartford Convention at the time of the War of 1812." Wiki "sorry but it was the fastest reference I could find."
And since that time there had been a movement, by certain peoples, to carry on what Thomas Jefferson had started, but with the larger intent of starting a new government without the Federalist, breaking up the Union and with it the oppressive laws created within.
The Civil War was fought to resist federal abuses to certain States and certain State's abuses to the federal...the right for self determination was the issue of the war- not the right to own human property. Secession was about breaking up the Union, slavery was the wedge to do it.