HG/SS
With tough opponents like Whitney, Morty, Clair and Red, plus Johto's awful level curve, these games are very difficult to Nuzlocke. The worst starter is Chikorita.
D/P
Diamond and Pearl are commonly called one of the hardest Pokemon games period, let alone to Nuzlocke. There's an extreme lack of Fire types in the region, making type diversity a little more difficult to obtain. Cynthia is also commonly accepted as the hardest Champion in any game, and she's all the more terrifying in a Nuzlocke. Turtwig is the worst starter in DP.
B2/W2
You don't get a whole lot of good Pokemon until later in the game, and types will overlap in your team. Cheren's Work Up Lillipup is a monster, Elesa is annoying as always, and Ghetsis is terrifying due to that Hydreigon. Serperior is probably the worst starter (seeing a pattern?).
US/UM (No EXP Share)
USUM were designed for using the EXP share, so playing it without it will be difficult. The Totems are all very tough due to the stat boosts, and Ultra Necrozma is a complete run ender. The hardest starter to use is almost certainly Rowlet (you may have noticed Grass types aren't all that in Nuzlockes).
Gen 6 games aren't very hard to Nuzlocke. XY have a large variation of Pokemon, and ORAS gives you a Latias, plus a large variety of Pokemon as well. Gen 8 is quite easy with permanent EXP Share, and the other games are similar but easier to the others I mentioned.
Hope I helped!
