Anything with a screen size bigger than 5" and flanked with buttons will start getting too big. A 7" screen would be even worse.And whatever it is it has to be under 1" thick. anything thicker start to feel too bulky.

If you wanna go as big as a 7" screen then it has to be a slider of some sort. But stil no bigger than 20mm thick. If going under or at 5" then it could be a flipper or have flanked buttons.

I this day and age, when so much people are comfortable lugging around huge phones, I think something like Wikipad is quite reasonable:

GBA original, the perfect handheld if we ignore the lack of light 

Also has something important new devices lack, which is it's thick. Makes a world of difference in grip.

PSP

You might like this design where they slicked in controls onto a phone that are flush, but still functional.

If we are going pure comfort to play

Otherwise I guess something similar too this with better clickable sticks and triggers (and games)

A vita with a clamshell design, 10 hours of battery life, and comparable specs to XB1 would be a perfect handheld for me

If the new 3DS had a real second circle pad, that would be it.