I understand that pathway gene lists in databases also include the inhibiting genes.  
Suppose I have a sorted list of genes, from high differentially expressed genes (hyper expression) through neutral genes to negatively expressed genes (hypo expression). When searching for pathways, should I submit one list with **both hyper and hypo subsets**? Are there insights to be gained when submitting each subset individually? 
    
What kind of pathways are you talking about? Please define. A metabolic pathway? Kinase pathway? As you can see already with my two examples, pathways can be very different and therefore differently regulated. In metabolic pathways, you'll have kinetics with enzymes, more expression of a gene might correlate with more of that particular enzymatic reaction, however some enzymes may also inhibit a reaction (so down regulation of some members of the pathway could be expected). So I would say, both up- and down regulated genes would be interesting is such a pathway. However for a kinase pathway, that is regulated by post-translational modifications, looking at up- or down genes wouldn't really make sense. So hard to give one answer, it depends on your definition of pathway.