I've shot many handguns that aren't in my collection, via rentals and friends, and my personal collection consists of 13 different frames and styles not counting duplicates. That being said I still somehow have not shot a Ruger .22 of any kind yet (seriously I don't know how that's possible) and a few others that have been mentioned here.
So out of my own experience thus far, here's what points the most naturally and easily/successfully for me:
For starters, my Nambu type 14 points
very naturally for me, in that I can look at something while holding the gun by my side, then close my eyes and point at the 'target,' then open my eyes to discover the sights right on point. I've never fired my Nambu however, so I guess it's an honorable mention as I can't speak for natural pointing vs POI.
So out of guns I own or have fired here they are starting with best
Believe it or not, the #1 on my list is my Beretta Tomcat .32auto. I can get very tight groups at 40 feet when using the sights, but I can seriously hit a milk jug full of water with every shot at 20-30 feet just pointing not using the sights, every time. I can barely believe it when I do it, as the gun is so small and I have very large hands, but I do it often and it just points incredibly naturally for me, like an extension of my will.
Next up would be my 1851 Navy .44 cap n ball replica. Using the sights it'll shoot a bit high for me, but when I just fire instinctively the targets get smashed with lead. I tend to tuck my pinky under the grip, and again the gun becomes an extension of my will.
Third would be my 1911s, they're just about tied with the 1851 but in a different way. Both of my 1911s have flat mainspring housings, and point very naturally for me, with or without using the sights. Strange thing is for me an arched mainspring housing actually points even better, must be my hands or something because for most folks I read here, it seems to be the opposite, but arched or flat, the 1911 fits my hand and points very naturally, again I can do the same -close eyes point at target open eyes- routine that I mentioned with the Nambu, and it works every time.
Last I'll mention my SAA's, they are very naturally pointing, but I tend to shoot just slightly high with them when I point vs using the sights. I have no doubt I'll correct this with more practice, but that's why they come in 4th on my list here