Suffering is a constant and fundamental part of human existence in Waiting for Godot. Every character suffers and suffers always, with no seeming respite in sight. The hardship ranges from the physical to the mental, the minor to the extreme. It drives some men to find companionship (so as to weather the storm together), causes others to abuse their companions (to lessen the suffering of the self), and for still others leads to self-isolation (since watching people suffer is a kind of anguish on its own).
Vladimir and Estragon suffer not for lack of happiness, but for lack of certainty. It is worse to not know whether or not they are miserable than to be certain of their anguish.