I think this comes down to "what are we fighting for?"
People say they lose interest because people all end the same and such, but in my opinion that is a symptom. The problem is that audiences lose interest because the show is treated a little too heavily with nihilism. Everyone dies, nothing good ever happens, there is no safety, there is no end. This can really grind on an audience's investment. The show seems to break down to a tale of survival, but that only works when there is light at the end of the tunnel.The fact that this is a tv show that will run, if allowed to, forever. Therefore, there can be no "end of the tunnel" the characters can never reach it or the show risks losing its central conflict. In my opinion, the show is at it's peak when there is something worth acquiring or keeping. For example, I loved the prison, no not the silly bits with the governor. The whole infection outbreak, I thought, was awesome. Sure it had it's problems, but the characters were fighting for something good. I could be invested because they were fighting for a better way of life, something they acquired through hardship. They were fighting for something worth protecting. Often the show finds its characters fighting for survival in a cruel and miserable world. That is dangerous. You can feed the audience nihilism, but it's on a ticking clock. With every second you spend on a bottomless pit of pain and misery you push the audience closer to apathy. A fight to stay alive is rarely very good in a show like this, because survival alone isn't enough. There is even a scene between daryl and beth earlier this season where the show points out that there is more to life than breathing, and the show bogs down when it loses sight of that. It leaves the audience asking, "What is the point if there is only pain and misery? is pain really worth fighting for?"