I see the Nemesis as the most pure self-defense folder made.
Some people think of a self-defense knife as a "fighting-knife" and they have visions of parrying an attacker's knife with their own knife, which means they need a guard to keep the attacker's edge from sliding down the defender's knife blade and cutting the defender's hand.
I don't care much for a guard intended for that function.
However, in reading an essay written by Colonel Jeff Cooper a few years ago, regarding the importance of the point of the knife, I found myself persuaded by Colonel Cooper.
I now believe a knife intended for combat, whether in self-defense or in the attack, must first have a point, and then an edge.
In other words, if I had to choose between an ice-pick or a straight-razor, I would pick the ice-pick.
Happily, the Nemesis provides both, but especially a point, and more so than on any other folder, to my knowledge.
In the case of a point, dagger, stilleto or any other edged-blade intended for thrusting, the user runs the risk of his hand running up onto the blade, especially if the point hits something that resists further penetration, such as a bone or body armor.
I consider this even more of a possibility in a desperation situation involving larger than humanly normal efforts.
In this regard, I see the Nemesis as having every imaginable erogonmic feature to maximize the power of the thrust in a desperation situation, and minimize the possibility of either the blade folding or the hand running up on the blade.
The Nemesis will serve well as a general purpose knife, but I think ER has optimized it as an anti-personnel/self-defense knife, and this includes the top guard.
ER makes other knives in this family that lend themselves a little more to general use, and they don't have the same top guard.
I see the Nemesis as a self-defense knife par-excellence, that will also perform various utility chores, such as cleaning a fish or opening boxes.
For those types of chores, I would hold the knife in the modified saber/paintbrush grip and the top guard would not get in the way.