If there is a main difference, it is in regard to the nature of government. In comparison to the Republican Party when it was first founded, the Democrats tended to be more slanted to strong state government and weaker federal government. That is, "states rights" supporters were more likely to be Democrats than Republicans, even into the mid-20th century. In the last fifty years or so, those tables have turned.
From the 1820’s to 1850’s the Democrats won all but two presidential elections. During the 1840s and ’50s, however, the Democratic Party, as it officially named itself in 1844, suffered serious inner strains over the issue of extending slavery to the Western territories. Southern Democrats, led by Jefferson Davis, wanted to allow slavery in all the territories, while Northern Democrats, led by Stephen A. Douglas, proposed that each territory should decide the question for itself through referendum. The 1860 election also included John Bell, the nominee of the Constitutional Union Party, and Abraham Lincoln, the candidate of the newly established antislavery Republican Party. With the Democrats hopelessly split,
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It established the Democratic and Republican parties as the major parties in what was apparently a two-party system. In federal elections from the 1870s to the 1890s, the parties were in rough balance—except in the South, where the Democrats dominated because most whites blamed the Republican Party for both the American Civil War (1861–65) and the Reconstruction that followed; the two parties controlled Congress for almost equal periods through the rest of the 19th century. The party at this time was basically conservative, opposing the interests of big business and favoring cheap-money policies, which were aimed at maintaining low interest