i don' even know if a print run of 20 should / would count as an official release but i guess it's a different debate altogether.
of mainstream systems, i still have to go with the turbo/pce route as being the most difficult. you have games that had low print runs (dead of the brain 1&2 and all of those hudson special editions), games that few want to part with (coryoon) , fakes to sort through (sapphire), games with lots of packaging (spine cards, posters, etc) rare accessories (try finding a SGX powerbase or pce speakers), and ridiculously hard to find/overpriced games like indo no honou which , the last time i saw it, was $4,500. (i have only ever seen it twice and i have been to my share of stores in europe, north america and japan). we can take money into account too but also TIME and availablility. there are many stores out there you could drive to and perhaps find that snes or genny game you were looking for. how many people ever carried and how many stores ever had turbo stuff? radio shack? the sears catalog? eb? toys r us? select kmarts? factor in the fact that lots of turbo stuff was wiped in when telegames usa ws hit by that tornado which destroyed their warehouse and the fact that whatever TTI bought back from retailers and/or couldn't resell had to be destroyed and it was a LOT of stuff. basically, whatever telegames usa and uk, tzd and the LA based turbo re-seller (whose name escapes me at the moment) and others didn't buy was destroyed.
so, as long as we are talking mainstream, the turbo/pce library takes the cake with the neo geo the more expensive (and there is SUCH a big problem with fakes there too).
if we leave the mainstream, then it's all just about impossible. there were only like 54,000 pippins even released in north america and japan. laseractive, pippin, cd32, marty, playdia- i would rank as follows from hardest on down:
pippin
laseractive
marty
cd32
playdia (i think i just completed my playdia collection this week but need to confirm it)
in the end, it depends on our locations, experiences, available funds, language ability (it's easier to find some stuff on jp sites if you speak the language) and so on...