Here is an image showing how I think the Endura 4 was designed to be held:

This grip creates multiple problems.
First, my index finger and middle finger barely have enough room to fit in front of the finger groove in the middle of the handle. They feel cramped and uncomfortable.
Second, this does not give me enough space to effectively use the thumb ramp. Again it makes my hand feel too cramped and my base joint of my thumb will hurt within a minute of hard cutting.
Lastly I have to shift my hand back to close it (I close Spyderco lockbacks one handed by swinging the blade shut with my index finger using the spyder hole, while pinching the lock release with my thumb). I do not have to do this with the E3 handle.
Here is another image, showing another possible grip for this knife:

This is worlds more comfortable. My fingers have enough space to be comfortable and my thumb has enough room to use the thumb ramp as intended. However, this grip also creates as many issues as it fixes for me:
Now the knife feels too blade heavy. This is especially noticeable on saber ground variants, but it also disrupts the balance of FFG Enduras.
Second, now my hand feels like its too far back from the cutting edge. The closer your index finger is to the edge, the better your control is, which is one of the many advantages of Spydercos index finger choils they often use.
So I'm just perplexed by this change to the Endura line. Neither grip works as well for me as the regular grip on the Endura 3 handle. The E3 got my hand closer to the cutting edge than the second grip I showed with the E4, while being 100% ergonomic for me.
What am I missing?