In short, the history of the Spinward Marches is one of waves of colonization followed by wars back and forth with the Zhodani Consulate, Vargr, and Sword Worlds Coalitions over the past millenium.
The Zhodani are the most powerful enemy of the Imperium in this region.
Actually somewhat more immediate as a threat are the Vargr, however they are disorganized, and so the threat they present tends to be more in terms of piracy or small-scale incursions (other than when they ally with the Zhodani for a major war).
The Sword Worlds are a violent confederation of humans that present a small, but constant danger.
Further afield, the Darrians are an advanced, and non-threatening race that controls a small group of worlds.