I agree with Redanman - nothing beats space between holes for safety! Trees, shrubs, and fences are second best.
Here is where safety limits my routings are as follows:
1. The Ross "fan shaped" routing. I tried to post this description last year, but for an explanation, see Forrest Richardson's book. Basically, we can't put clubhouses, or even hole clusters in corners anymore, because we take up more space. Those tight corner clusters of tees and greens really help get change of directions in routings. But, they put high intensity areas, where you might pick off four golfers (and up to four caddies!) with one shot, as opposed to randomly hitting just one golfer!
2. Tree preservation. I often find a tree about 200 feet from the property line, in the landing zone. Then, I must decide, do I push the hole "below minimum" to the property, or take out the tree?
Knowing some court cases are decided with printed "Standards" of how close a hole should be to a property line, let's say 150 feet (or 175), I often opt to axe the tree. Similar situations exist between parallel fairways.
3. Lining up holes. There is a preference for lining up holes for safety, which further straightens routings. Furthermore, it helps if landing areas are "beyond" each other, so wayward shots fall well short of intense play zones.
I have found myself actually reducing my previous minimum distance between greens and tees, if the next tee is behind the green, for greater walkability.