As someone who damn-well worshiped the PS1 Resident Evils, all the up to Code Veronica, I will submit RE4. Is it a great game? Sure. Is it Resident Evil? No. The original Resident Evil 4 was actually turned into Devil May Cry. What we got was a new IP with the Resident Evil universe slapped onto it, ala SMB2.

This has been my wildly unpopular opinion since it launched on Gamecube, and it will always be my opinion. lol

Worst: Resident Evil 4. It effectively killed a unique genre. Signalis feels more classic RE than any actual RE game since Zero. It was almost like going from FF10 straight to FF16.

Best.  Front Mission Gunhazard. Series is normally a SRPG where Gunhazard made it a side scrolling ARPG. It plays like most side scrolling SNES mecha games but it has RPG elements and a Super Mario Bros 3 overworld. The OST is phenomenal and some of it sounds like prototypes for FF7 songs.

WORST. DmC Devil May Cry. What a giant giant turd. The edglordy cringe tone and dialogue are made by a mid life crisis edglord moron for edglord morons. The dumbed-down combat. Until the day I die, I will piss on this piece of shit's grave and am so glad the real DMC is back. With Kamiya doing Okami and he expressed interest to remake DMC1. I welcome back the king.

I like Starfox Adventures. It's a fun zelda-like. But it's not as good as Zelda and not what the series is known for. 

Best: Warcraft 3. Turning a strategy series into a strategy RPG was so great, it spawned a new game genre with dota-like mobas. And the game was near-perfect.
Worst: FFXI, the moment I stopped playing my favorite video game series. I know it was huge and people were addicted, but turning FF into a MMORPG started the downward spiral of the series for me. I only played 12 after FFX for 5 minutes, that's as far as I got in FF after X.
Honorable mention: Wind Waker, the moment a part of my inner zelda fan died. Zelda was not a series for kids, it was for everyone and a cool series that has a great aesthetic. WW ruined that during an era when Nintendo was competing with huge PS productions like FFX, which looked incredible.

Wind Waker was too easy and also failed to provide a GOOD ending part of the game. Very mediocre last part. I always thought that game needed a 2nd disc, or was maybe projected but cancelled. The Triforce parts search was stupid, boring and monotonous. After Ocarina, they could perfectly avoided its search, no need if it had to be so boring
But the freedom that game gave you in the open sea and that music, especially the first time you played it... to me was amazing. The toon style was a bad decision. Probably a good idea for a future game, but everyone wanted a next-gen "mature" zelda in 2001 (like the demo they showed in the last Space World in 2000). Was a half-baked game and its art style was very attacked during many years. Now, nobody cares anymore though, but then... my god.

But for me, Skyward WAS the HUGE disappointment. That game... sucked. In every aspect. including the search of Triforce, again XD. You got it ALL (ALL the Triforce, not parts of a part) in just

S-T-U-P-I-D.

Stupid like the story, the art style used (that was just poor cheap graphics, not the "realistic/toon mix a la Monet" as they tried to sold XD), the flying parts, the races, the faces, the supporting NPCs, the main NPCs, the islands (barely populated with NPCs with "no life" feeling, very very old style NPCs), all the sky in general, the non real-time changes of daytime, the useless night time, the bad guys, THE REAL BAD guy... all very stupid. That game was a fake Zelda. The dungeons were not that bad, but not that good either if you already played many Zeldas. What a bad excuse to just sell a gimmick (the Wii motion plus). It was a disastrous game for the series. Maybe not bad as Triforce Heroes (the following one) for the credibility of the series, but for sure both preactically killed huge part of the fanbase created after Ocarina, at least for some years.

The best? Breath of the Wild. It was like Ocarina, but x10?,... x100? times better in ALL aspects, and with loooooots of promised and not delivered things 20 years before finally coming true... with many other new and never promised features before... also coming (like a real huge mainland FULL of everything including trees and even real forests with animals... everything usable, or horses living in the wild waiting to be domesticated, or real weather changes everywhere, or none loading black fade-outs entering towns or houses, or people in towns being around in a credible and "living" way, or NPCs traveling from town to town in real time using the roads.... And man, those physical superpowers where just amazing, new and unexpected,... and i could be on and on... all day along.

MANY MANY MANY things the old Ocarina could not possible display in 1998, for technical limitations, and many more never promised before, all included. For the first time, a Zelda forgot to copy the very old and already decrepit Ocarina standards after almost 20 years of being reused in EVERY ZELDA 3D GAME, and they did a brilliant new Zelda full of new technical details and amazing possibilities. And at the same time, being a monumental act of recognition to that same Ocarina that changed so many things in its launch, and older fans enjoying decyphering it. Also, beautiful and great story, fantastic music and sound production, and great NPCs. What a perfect Zelda game... just in a critical moment for that series.

This doesn't count, but that Bomberman artwork made me want to mention the Megaman 1 and Megaman 2 boxart.

Because they actually turned the former into a playable character in Tekken vs Street Fighter.

And they made him fat.
But that's not an entire game direction.

So the one that came to mind first was Breath of Fire 6.

Because they turned a beloved jrpg series into a free-to-play online, web-based multiplayer role-playing game with microtransactions.
Keeping the 6 in the title to market it as a mainline entry seems especially cynical towards fans that wanted to see a sequel after 14 years.

As for the best?
RE4 is probably my answer. I also think RGG Studio really nailed the transition from Yakuza's brawler style gameplay into a turn based rpg. Although most of everything else remained the same.

Lol this is first time I've ever seen it.

For me:

Best, probably God Of War prehaps, the fixed camera action thing that was 1 2 and 3, never gelled with me, I played 2 only, can't even remember much of it. So the relaunch as a more 3rd person adventure? Very nice. Have not ever got around to getting Ragnorak though, really should. Maybe in the new year.

Worst, well DAV being an action game is right up there, decent game, terrible DA game. And obviously Final Fantasy, I haven't purchased a new FF game since 13.

I actually enjoyed Skyward Swords. 

The motion controls really added something new. The music was great, told a great prequel story and the art style is what inspired Breath of the Wild aswell as the stamina meter etc.

It was different but playing the HD remake made me admire it more.