D&D 4th Edition
4E, being my current favorite edition of D&D, was a natural. I love the tactical gameplay and the powers, but it's also a very crunchy game. As I don't currently have a DDI subscription, I don't have access to all the dozens of classes and races, hundreds of powers, or thousands of feats that 4E has available. Every time I create something for the game, I'd have to be wondering if something officially published might already be doing that job better than I did. Also, I'd have to consider why someone would take a new race or class when they could take something that's already extremely well-supported.
While those may not be the best reasons to avoid using 4E as a system for a new setting, there is at least one more reason why I was hesitant to use it: difficulty. I haven't had much success fiddling with 4E, and even though I've run several games of it, I don't know that I have a handle on the rules well enough to go tinkering around with it without having a better idea of what my tinkering would do to the very tight math and solid game balance.
Still, 4E is my favorite D&D so far, so it was never completely off the table.
In contrast to D&D 4E, I've already had some success tinkering with Savage Worlds. I've run it several times, the same as 4E, but I played around with creating custom races and modifying spells with Trappings and adding in Ritual-style magic.
I also like that Savage Worlds is a much quicker game. I want They Came From the Stars to feel more like an Indiana Jones or Star Wars film, with a lot of fast-paced action. Though 4E excels at battlemat combat, it also takes a long time for combat to resolve, where Savage Worlds can get into combat and be done in maybe twenty minutes at the longest. Honestly, it doesn't hurt that I find the Savage Worlds Deluxe Explorer's Edition to be much faster and easier to flip through for reference than most of the 4E books, and everything I need can be found in just that one book.
In the end, I decided on Savage Worlds, though I will be incorporating some 4E-style elements. I really like how 4E handles ritual magic, so I'll be incorporating a similar system for magic like long-range teleporting, scrying effects, and controlling voidships. I also liked the 4E take on traps as static enemies in combat, so I'll almost certainly be bringing that to Savage Worlds in one form or another. All in all though, I enjoy tinkering with Savage Worlds more than I do with D&D, so hopefully that'll help keep my motivation and inspiration up for They Came From the Stars.