For me, the hardest part is the setting, not the rules
I run a 5e Shadowrun game.
The hardest part of 5e is not the rules, it is the lack of adventure support. Shadowrun, in any edition, has fairly complicated rules, with lots of combat detail. However, that's not what (for most players in my experience) the game is about. Hack and slash in the game gets boring really quickly. The game is really about the baroque interplay between the various major players in the world. The game is about the plot twists and turns. To be blunt, I have yet to see a GM do this nearly as well as the majority of the published adventures for previous editions. I myself, who have no problem putting together adventures for D&D or Deadlands, prefer to use published stuff for Shadowrun for this reason - a writer who has time to do ti right can do a better job with the plot than I can.
However, 5e doesn't have a stock of adventures to use, and more are coming out only very slowly. I an considering having to go back to my stock of 1e and 2e adventures, and retool them for the current edition.
The matrix and magic is hard to figure out and use consistently in game. The hacking rules is probably the hardest part for me, which always require that I check the book to remember how it goes.
Well, I skipped some of the middle editions, but 5e has fixed a major part of hackers - they now can play a support role in the physical world, and a great deal of the information gathering they do doesn't need a full matrix run like in older editions. The basic mechanics of what they then do are simple, and easy to remember (or put on a chart) so a good chunk of the time, you don't need to remember the fullness of their rules.
As for magic, going astral is no longer as common as in previous edition. That's a great thing in my book.
I think that's group-dependent. My players do it all the time for scouting.