When I watched Gurren Lagann for the first time I was about 14 and I think that colors my perception of the series a lot. It's grand in scale, but basically just a coming of age story.
I was emotionally devastated by Kamina's death because he was just so cool and everything I wanted to be. I even thought he was the protagonist and Simon was just sort of a normal kid along for the ride.
Then gradually Simon matures into someone that can not only fill his shoes, but surpass him, culminating in the climax of the series where Simon talks to Kamina again. We find out that Kamina was more or less a buffoon carried by Simon all along, and had more value as a symbol than anything else. Simon is an adult, with responsibilities beyond a vague notion of rebellion, and the whole world on his shoulders. After this meeting, he rather handily defeats the anti-spiral in the denouement. He accepts the task of protecting the cosmos on behalf of humanity as the price of freedom, paralleling the burdens we take on as adults.
It's a simple and not particularly original story, but still compelling because it's about the human experience. This is just my favorite interpretation of it because it has giant robots and Yoko tits.