My contributions:
Misty in R/B and FR/LG. Yeah, give the second Gym Leader you fight one of the best, most well rounded Pokemon in the game as well as a hugely powerful (at the time) STAB move to destroy you with, which in FR/LG can also hax you out with confusion. I swear I either have to get an Oddish or paralyse the Starmie with Thunder Wave every time I fight her she's that bad.
Whitney. Her Miltank's awful in both the original G/S games and the remakes, for abusing its gargantuan bulk with Rollout in the former, and generally being a long lasting prickette with Milk Drink in the latter. Oh, and she has a Lum Berry in the remakes, meaning if you try paralysing her, it's just a waste of effort and will get your Flaaffy killed. Most of the time I just get a Selfdestruct Geodude to deal with her ass.
Clair, especially in HG/SS. Anybody who started with Cyndaquil will get absolutely trashed in this fight, all of her mons resist your STAB, her star by 4X. She's MUCH worse in HG/SS, as not only did she get a very slight level buff and one extra Pokemon in the form of Gyarados, but her Kingdra got a much stronger Dragon attack in Dragon Pulse, a huge upgrade from Dragonbreath. Not even forgetting that you most likely won't HAVE any Dragon attacks of your own by this point, meaning that you can't deal with Kingdra via type advantage. UGH.
Ghetsis in B/W1. Oh boy, he has a really weird yet effective team. Things like Bouffalant and Cofagrigus which can cripple/kill you and are nearly impossible to OHKO are bad enough, but Hydreigon, DEAR GOD that thing is ridiculous. It has a really trollish ingame Speed tier, meaning unless you have a Musketeer or something like Whimsicott, you likely will get outsped and destroyed by its supreme type coverage. It's a shame that Ghetsis was so much easier in B/W2, I mean physical Hydreigon, level downgrade, TOXICROAK? It's really sad actually...
Cheren in B/W2. I only really put him here since he's the only Gym Leader or E4 member I actually lost against, and it's only because he got to +6 with Work Up while I was spamming Counter with Riolu hoping for him to attack me. Quite embarrassing. X.X
Iris in B/W2. A lot of people say she's easy, but I had an entirely different experience. Her team was pretty easy to beat except for the 2 holy grails of Dragon Types in Hydreigon and Haxorus. The former is not only her LEAD, but unlike Ghetsis' is actually given a competent moveset and functions in pretty much the same way B/W1 Ghetsis' does in considerably whittling away at your poor morale one little bit at a time. While battling her I had to sacrifice Flygon and then bring in Lucario to deal with the bastard while Iris Full Restored. Haxorus however was surprisingly the hardest part of the battle. I aimed to do a Swords Dance Lucario sweep of her and took down Druddigon Lapras and Aggron like dominoes, until Haxorus came in, outsped and KOed with Earthquake. From there, it Dragon Danced and proceeded to tear my poor Pokes apart with Dual Chops from hell, and I would've been swept then and there if the AI wasn't retarded and tried to do a second Dragon Dance against Flygon.
I'll also embarrassedly admit that Skyla gave me a little bit of trouble on B/W2, as I had no Electric type moves with my super limited team, and Swanna outsped Vibrava, KOed it and Featherdance stalled Lucario and Crobat before KOing them as well. Fricking SWANNA of all things came the closest any Gym Leaders' Pokemon came to beating me in my B/W2 runthrough, well except for Cheren's puppy.