George is silently grateful to have a companion in Lennie but Lennie's tendency to get into trouble is a serious detriment to George's attempts to make a better life for himself. Since it is their goal to save money in order to buy their own land, it stands to reason that the longer they work, the more likely they will raise that money. However, Lennie repeatedly gets into some trouble and forces them to seek work elsewhere, thus beginning the plan to save money all over again. In Chapter 3, George recounts their last bit of trouble in Weed where Lennie panics and holds on to a girl's dress:
The guys in Weed start a party out to lynch Lennie. So we sit in a irrigation ditch under water all the rest of that day.
When Lennie accidentally kills Curley's wife, George has to find a way to fix the situation. And this time, the only solution is to kill Lennie. George feels responsible for Lennie's actions, so Lennie's mistakes are indirectly his. That's not to say that George is to blame in these instances but George does take responsibility for them. Since he takes responsibility for Lennie's mistakes, they are George's as well as Lennie's defeats. George is defeated by Curley's wife's death and he is defeated in a more fundamental way when he has to kill Lennie. George probably realizes this was the only way to break the cycle of Lennie's unwitting destruction, but George was Lennie's guardian and he feels that he failed in this occupation.
The last image we have of George is when Slim takes him to get a drink. Slim is being a consoling friend but there is a larger implication in this gesture. George had always been faced with the sporadic nature of being an itinerant ranch hand but had been determined to save some money. He tried to avoid wasting it at bars and brothels. Walking away with Slim to get a drink at the end of the story; this symbolizes George's defeat and his (at least temporary) acknowledgment that he might as well waste money on the drinks since he might never get that piece of land.