Older protagonists, the female PC's design, the first female professor, triple battles, two rivals (three if you count N), idle animations, online random matches, portrait cutscenes with moving lips, no more NPC Roadblock, and specifying the weather on the bottom screen instead of pausing every turnto remind you.
In the old days, TMs broke after one use. Not anymore! This allows the creators to introduce (in some cases, such as Rock Smash, re-introduce) the more "useless" HMs as TMs, which means that Pokémon can finally just forget them if necessary without the player having to look for someone to make them forget the attack. On the other hand, TMs were made more expensive in order to counterbalance this.
Although Woobat takes Zubat's place, it's much less of a Goddamned Bat than the above three were. Woobat tend to buff themselves or confuse the player's Pokémon, which means no harm, no foul if you simply run.
There are 156 new Pokémon. That's more than have EVER been introduced at once in a generation.
Tornadus of the Kami Trio is the very first pure Flying-Type.
And there is now a fully-evolved pure Dragon, Haxorus (all previous fully-evolved and Legendary Dragons have been dual-types).
And a non-evolving pure Dragon-type with Druddigon.
As well as the first three-stage pure Ice-type line (Vanillite, Vannillish, Vanilluxe) and the first pure Steel-type evolutionary line (Klink, Klang, Klinklang).
Only six HMs are in the game, including Dive for the first time since Hoenn.
As a bonus, aside from an early instance of Cut, (which one could teach to a Patrat or Purrloin, or the elemental monkey if you didn't intend to keep it beyond the first gym) none of them are needed to finish the main storyline. Meaning the only move slot you'll "need" to waste is that of a flying type for the Fly HM for convenience's sake.
Vanillite, Vanillish, and Vanilluxe, the ice cream Pokémon, was enough to convince many on the fence to fall in love with this generation.
There was even more rejoicing when a remix of Blue Oak's theme from the original game was revealed.
In the Pokémon League, when you fight the Elite Four. Not only do you fight them, you also fight the Version Exclusive Legendary, Zekrom/Reshiram, the leader of Team Plasma, N and then his father, Ghetsis. You fight the champion after getting the National Dex.
Mewtwo finally gets its very own signature move, Psystrike.
Stealth Rock, the move that had reshaped the metagame in Gen IV, is no longer a TM.
Most routes now have a NPC that will heal your Pokémon on the spot, negating the need to head all the way back to a Pokémon Center for healing. Previous generations only had occasional healing locations on longer routes.
There are a lot of trainers who can be fought daily for experience besides the Elite Four. This makes it a lot easier to both train Pokémon and get money.
The Gym Leaders actually DO SOMETHING about the evil syndicate instead of letting the hero do all the work, including arresting Team Plasma Members and assisting you in beating them. Then in the endgame, they pull a Big Damn Heroes moment and perform a You Shall Not Pass on the Seven Sages to let you go on ahead.
Generation V (Black/White and Black 2/White 2 alike) also feature a welcome addition: box-to-box Pokémon trading in Local Wi-Fi play. That's right, nobody'll ever need to get out of the Wi-Fi Room and swap the Pogeys in his party with those in the PC anymore.