Nuzlocke Difficulty Rankings (Updated July 2020)

1. Ultra Sun & Ultra Moon (no EXP Share)
Likely the most aggressively difficult vanilla game, due to a combination of harder totem fights (totems such as Araquanid and Marowak can handle or even beat some of their main counters; partners are better and make an effort to support their totems) and perfect IV/EV boss fights. On top of that, SuMo's lackluster Pokémon distribution (even with the new additions) locks off potentally useful resources prior to totems that they're best with and good 'mon are often hard to find or late in the game. The curve on this game is also properly designed to handle EXP Share, meaning you will not be in a great place even with it on, and turning it off just makes things even worse.

2. Black & White 2 Challenge Mode
Consistently high difficulty + heightened level curve = no fun. Limited capture areas, especially before Castelia, make team building particularly difficult. You won't have a full team before Roxie and there are very few Pokémon you can access that will help you with the first 3 Gyms. All gyms are given an added Pokémon and the existing Pokémon are generally improved. (See BW2 Normal for further explanation)

3. Platinum
Improved version of DP spikes the difficulty significantly. Nearly all plot battles (from Mars' Fat Cat to Cyrus's death squad) are difficult and common 'mon death points. Last 3 rival battles are sudden and difficult. Monster distribution is somewhat poor in the early game and the revised order of the Gyms with Fantina first makes a harder lineup, particularly due to lacking good resources for these gyms. Gyms after 3 have beefy and hard-to-counter teams. Improved E4 has a huge variety of awesome Pokémon and Cynthia packs an even more challenging team.

4. Sun & Moon (no EXP Share)
Totems as a concept are fairly unfriendly to Nuzlockes and most do not have hard counters. Pokémon distribution is somewhat lackluster and doesn't always provide useful tools prior to Totem fights. Boss fights also tend to be fairly difficult due to perfect IVs, with even early game bosses being sources of wipes. Less aggressively difficult than USUM due to a less ridiculous end game and easier trials/totems/bosses overall.

5. Black & White
Early game is pretty difficult with limited team members and no guarantee of useful captures. Although slightly less awful than some parts of BW2 Challenge, the leaders will likely kill at least one of your Pokémon. Also has a limited number of areas where Pokémon are catchable. The final battles are also extremely difficult and tend to be choke points.

6. Black & White 2 Normal Mode
A lot of the same problems as BW2 Challenge and BW, but without the insane curve on levels and easier early Gym Leaders. Ghetis battle is easier than in BW but Corless battle is fairly difficult and Plasma Ship sections can be tough.

7. Emerald
Still relatively challenging but the curve doesn't start until after Gym 2. The middle leaders are troublesome and Tate & Liza are very difficult, and Archie/Maxie fights are more numerous and difficult. Though the E4 is probably easier since Wallace is an easier champion than Steven, the increased difficulty of the Gym Leaders and story battles make it somewhat harder. Grinding is also particularly tedious.

8. Omega Ruby & Alpha Sapphire (no EXP Share)
Although essentially the same as the original games, the level curve has been rebalanced for EXP Share, so turning it off will mean you fall behind much more quickly. The reshuffling of story fights and addition of Megas also makes it a bit trickier to keep up with (though your resources are also improved).

9. Sun, Moon, Ultra Sun & Ultra Moon (with EXP Share)
SuMo and USUM are much more balanced for EXP Share than Gen 6 games, so you're less likely to overlevel, but the increased leveling rate will make the games overall much easier. Totems and early game being generally challenging means that even with a more even level you aren't guaranteed to have an easy time.

10. HeartGold & SoulSilver
Through Lance, HGSS are fairly easy. There are a few sticking points before Indigo (Morty, Jasmine and the Rocket Hideouts come to mind) but the E4 is relatively low leveled and has only so-so teams. Post-E4, however, gives you nine high-level difficult battles without any source of low-risk grinding as well as one of the highest-level and hardest battles in the franchise in Red. Also easily the longest game in the series. If you're only playing to the E4, it's likely the easiest, but if you plan to do the whole game, Kanto and the overall lenght make it tougher.

10a. Gold, Silver & Crystal
Considering HGSS is nearly identical to Crystal in plot, battles and pretty much everything else that's not graphics, they're roughly the same difficulty. The only major difference is the Kimono Girl battles, which are later and somewhat harder in HGSS.

11. Diamond & Pearl
Much easier than Platinum due to a lot of Pokémon omissions that make Gym and E4 teams much easier. Order of the Gyms also gives a little cushion and an opportunity for mid-game team building and grinding. Story battles are still difficult, though teams are slightly less hellish. Cynthia also has a harder team and a harder Garchomp.

12. X & Y (No EXP Share)
With such a diverse pool of Pokemon, it's incredibly easy to end up with a team of incredibly weak Pokemon, especially early game. The gyms aren't too bad, but the story beats can be surprisingly difficult and some notorious NPCs can easy end a run if you're not careful. Due to the diverse pool in X & Y, it's easy to miss out on the opportunity to mega evolve, especially if you lose/refuse to use the Lucario. This can make many of the late game matches challenging. It's also hard to grind since there's no traditional EXP Share option to get under leveled Pokemon battle ready. It's really up to whatever team you can build that dictates this one's difficulty.

13. Ruby & Sapphire
Same issues as Emerald though the Gyms are generally easier overall. E4 is harder because of Steven though only marginally so.

14. Red, Blue & Yellow (and Green)
Breakability of the game increases the ease significantly, though many of the sections may still be challenging (e.g. rival battles, Giovanni fights). After Misty, you can essentially skip directly to Koga if you want, allowing you to gain a lot of EXP fighting trainers and doing Rocket buildings before fighting Gym Leaders. RBY ranks above FRLG only because of difficulty with grinding and the fact that RBY's mechanics are so insane you're more likely to lose Pokémon to hax. The E4 is somewhat challenging but many repetitive teams make for easier sweeps. The final battle is also one of the more difficult but it is similar enough to earlier battles that there should be some level of familiarity going in.

15. FireRed & LeafGreen
Somewhat less breakable than RBY but still allows for significant sequence breaking and few major sticking points. Vs. Seeker grinding also eases some of the problems the game has with levels, making it somewhat less stressful. Gen III moves and TMs also make many more Pokémon viable, meaning captures that would be shit in RBY may be better in FRLG.

16. Omega Ruby & Alpha Sapphire (with EXP Share)
Just as unbalanced as X & Y, though lacking some of its benefits like insane 'mon diversity and stupidly easy Gyms are not present, as well as somewhat more difficult boss fights. However, EXP Share still keeps you at or ahead of your foes' level, making it fairly straightforward.

17. X & Y (with EXP Share)
Once was unquestionably the easiest Nuzlocke. With the EXP Share, you will always be on par with or over your opponents in level. Pokémon population is wide and diverse, normal trainers are generally manageable and have few Pokémon, leaders are low-leveled and have between 2 and 3 Pokémon max, the E4 and Team Flare are all relatively simple battles. One the easiest Nuzlocke to complete with no fatalities, though turning off the EXP share increases the difficulty substantially.

18. Sword & Shield
Undoubtedly the easiest game in the series to Nuzlocke. Since the Wild Area appears to early in the game, you can nearly fill a box with encounters before the first gym. The EXP Share can no longer be disabled, making it incredibly easy to end up overleveled, even if you avoid all trainer encounters. None of the gym leaders pose a threat unless you refuse to Dynamax, and even then it's particularly easy to wall most Dynamax encounters. While it's customary to avoid EXP Candies, those who don't can find themselves 20-30 levels higher than the in-game NPCs just by doing raids you find on your own. Since there's no way to turn off the EXP Share, any difficulty in the game needs to be forced with additional rules.