The Necklace alone is too small. It's a single system with an amazing setting, but there is not enough variation. Otherwise, it would be perfect. I could flesh out the region around the Necklace's star system, and that could be very interesting.
The old StarCluster 2 setting could be revived. It's too big as is, but some small portion of it could be used. It would feel like a retreat though.
I could create a setting specifically for SC4.
Jeshen Space - a setting I created for my IRC game - might be very usable. It has humans as the second species, allied to the Jeshen - an extremely humanoid species, whose apparent similarity to humanity masks a very different evolutionary trail.
Jeshen are almost exclusive carnivores, small, hairless, with a powerful tail they use in swimming, semi aquatic, hermaphroditic, with amazingly good eyesight and slick skin that will not wet. Otherwise, they look very human indeed. It may be parallel evolution, or it may be that they or humans were designed to look like each other by a third party. This would be left open.
In any case, Jeshen Space is mostly surrounded and threatened by space controlled by another alien species, one which detests both human and Jeshen. There have been several wars with this other group, which the Jeshen-Human alliance has so far been able to stave off. There are continual pokes, prods, and 'border incidents' now, though not actual warfare.
I could also include the Necklace into Jeshen Space with very little change...
And a link - a long, difficult link - to human controlled space as well, room for further expansion...
What do you all think?