Tales of the Shattered Earth
This is a D&D 3.5 game that is set in a fictional, home brewed amalgamation of the Core rules, and the Lords of Madness settings. The overall theme is one of vastly powerful alien entities wreaking havoc on the world, and a small band of heroes who start incredibly young, making their way to stop the vicious creatures.
This is a second re-imagining of an earlier campaign setting where I did something similar, though I feel I advanced the characters and story too quickly both times (getting better each time). So, this is try the third!
We may also delve into other systems with this setting depending on how things go.