What was the largest and most constant issue facing the united states during the era of manifest destiny?

It was the quest for westward expansion. The Manifest Destiny called for the US to fulfill the divine mission to expand and dominate the whole continent. After the independence, the US moved westward step by step: the Louisiana Purchase, Texas, the Mexican-American War. This last event allowed the US to increase its territory, incorporate California and reach the shores of the Pacific Ocean.