New ideas - or a fresh look at old ideas. Don't try to be different merely for the sake of difference. Instead, come up with a small number of cool concepts to base your setting on, and then consistently work out the consequences of these concepts.
If you invent every single small thing anew, then you will alienate potential players - because they have to learn every small detail about your world to make sense of it. If in doubt, it is better to be logical than to be original - because worlds where people live in (such as the PCs) have to have an internal logic. It's better to discard a really cool idea when it doesn't fit into the rest of the world...
What I am not looking for is a gazillion new prestige classes, feats, and so on. Sure, it's allright if your setting has some of those - but they should follow naturally from the setting, and not the setting from the new rules.