Complete isolation is the ultimate threat in Endgame. It is a large part of what keeps Clov from leaving Hamm, and it is what keeps Hamm clinging to Clov and Nagg. There is, in a sense, competition between the characters as to who feels the most isolated. Hamm threatens Clov with isolation, saying that it will be even worse for Hamm than it is for Clov to be alone because he will not have a servant to take care of him. Nagg wishes total isolation on Hamm so that when he calls for Nagg it will be out of necessity and not just because he feels like it at that particular moment. The play closes with this impending threat of isolation for Hamm. He is about to be left alone, wheelchair-ridden and blind, with only himself for company.
The characters speak to each other so harshly because they are all so afraid of being abandoned; if they form attachments, then it will be that much harder when they are ultimately left to their own devices.
In the play, isolation is a greater threat than death. The way that the characters cling to each other keeps any of them from being able to bring about an end.