I personally prefer the middle two (middle & ring)
my middle knuckle is significantly taller than my other knuckles
i refuse to do the old style karate training of flattening the middle knuckle, so..
if I go the first two knuckles (index & middle), i have to over pronate my wrist to make contact
if i go the last two knuckles (ring & pinkie), my pinkie's likely to shatter
the middle two is a happy medium that helps me get power, keep my structure, and not risk too much damage

that being said, if i throw a hook with the fist horizontal, i'll try to land with the first two knuckles - i do that to ensure that i don't accidentally catch my pinkie and break it.
sometimes, i'll land with the first two on my cross as well - coming from a southpaw angle, many times my target is more on the thumb-side than the pinkie side so I don't have to pronate the wrist.

Dempsey recommended the last 3 (middle, ring, & pinkie)
Frazier and many others recommend the first two (index & middle)