I'd say the Tex Murphy series. Before you dismiss me as a fanboy for banging on about those games in every thread without failure, I have my reasons.
I'm sure that the Fallouts (among my favourite games of all time) bring a lot of people to GOG, especially after the launch of FO3 and NV, those games have always been available in retail on online (i.e. Amazon).
Access was bought and shut down by Microsoft a long time ago. I still had my original Pandora Directive CDs, but getting them working on a modern system was a bitch (not impossible, just a bitch, especially the sound). Not to mention that you couldn't find them anywhere but in eBay. Not to mention the annoying CD-swapping for a 6 CD game (you could bypass this by ripping each CD onto your HDD, creating 6 virtual drives and changing the .ini to read each CD from a different drive, but once again - effort). Also, I had not been able to acquire Overseer before and I had been unable to finish UAKM because one of my CDs had become scratched.
I remember when GOG was first launched and I remember all the publicity it got in the beginning and with the addition of the Fallouts, etc but I never bothered to join. One day by accident I found out that they had the Tex Murphy series and I joined immediately and without losing a second. I actually had to badger my girlfriend to buy me the games because I was out of money at the time. Thanks GOG!
TL;DR I don't think it's the so to say 'classics' like Bioware RPGs, etc. I believe it's the rare games from defunct companies that are now unobtainable through conventional retail, or which are extremely difficult to get working on modern systems