The difficult life of coal-mining
Kentucky residents know too well just how gruesome a career in coal-mining can really be. Besides the basic threats, lung cancer and pneumonia for instance, and besides the frequent mine accidents, there is another threat: when the mine is finished producing, people like the novel's cast are left even worse off, established in a town that is doomed.
The pitfalls of religion
There is a sense in which Ruth's Christianity has been darkened by her desperation. She desperately wants to believe that she can depend on God for some sort of breakthrough, but there are two main indicators that her religion has failed her: her son has rejected her view of the world wholesale (not a sign of a healthy, functional relationship), and also she eventually chooses death for herself and for her son, perhaps an attempt to "curse God," as the Bible puts it in Job.
Hopelessness
The main defining quality of the family in the novel is that their station in life is completely immobile. Not only are their main options 'servanthood' and 'coal mining,' but also, the society is regressive and oppressive to minorities like Andrew the gay son of Ruth and Earl. Then, to drive home just how desperate their situation really is, the mine shuts down (not uncommon in mining communities, since it's hard to know how much ore there will be in the future). The last signal of hopelessness is Ruth's indirect suggestion that Andrew has killed himself.
