I have pretty small hands, and several sizes of spydercos, and a full sized griptillian. I think the big factor is the fit. Exactly how your hand falls naturally onto the handle as well as where the hole sits, even dexterity and where your grip "feels" strongest is going to be different for a lot of folks. Some of us are going to have a range of motion that means the sweet spot is larger, and some are going to find the uncomfortable edges a bit easier. Between the different spydercos, I've had two different sizes of lockback (native and dragonfly) two different compression locks (Para 3 and Caribbean) and I have had several "axis lock-like" SOGs, but my main comparison to my Grip is a Bugout (thumbstud). So using that venn diagram of what was comfortable, and how the lock interacted with the opening, I think that overall, the fit to the individual is going to determine if your hand falls into the opening sweetspot, but the lock will have a minor effect on how wide that sweetspot is, with the added compromise of easy opening, vs. blade retention. For example, my Native is harder to open than my Grip, but to my hand they are both right in the sweetspot, so its almost imperceptible, but certainly the native is never going to pop open a bit, where while not common with the grip, it's been documented.