There were a number of factors that caused these problems. Let us look at two of the most important ones here.
First, a major factor was racism on the part of the white settlers. (If the Indians were racist, it had much less of an impact since they lacked the power to act on any racism they may have felt.) White Americans tended to feel that the Indians were inferior to them. Therefore, they treated them in ways that were sure to bring about conflict.
Second, there was the simple fact that so many white settlers were coming in to the various places where the Indians lived. The fact that there were so many whites meant that they were constantly going to need to move out into Indian lands. As the population grew and grew, conflict became more and more likely.
I should note here that many people would talk about different conceptions of land ownership between the whites and the Indians. They would say that Indians did not believe in owning the land where whites did. However, I would argue that this does not matter much. Even in places where (as with the Cherokee and other tribes in the Southeast during Indian Removal) Indians did believe in land ownership and sedentary farming, there was still conflict. Whites still wanted the Indian lands and were still willing to push the Indians out to get it.