The game is unfinished and cut short. You get Eli and Psycho Mantis running away with Metal Gear and the 3rd strain, and you get no conclusion. You have to watch the rest on Youtube from the LE that they gave out.
https://www.youtube.com/watch?v=6u45Z4QpP-g
The game clearly was planned for more. You have chapter 2 which is filled with old missions on higher difficulty to fill the void. The problem is we'll never know how much was originally planned. Ending it at Mission 51 on the Eli and Psycho Mantis fight could work, but it sounds like they wanted to go even further. There's the whole thing with Konami firing Kojima due to money issues. Exhausting the budget and wanting the game out the door, it's unfortunate that it ends this way. There's other cut portions that were shown in trailers. Even data mining, we found unused dialogue for the ending among other things.
Venom Snake twist. A lot of us saw this coming if you watched the trailers and followed the game closely. This was an MGS2 twist done poorly. MGS2's twist at least expanded on the implications of what's real and what isn't after the revelation. It was a plot point. You being Venom did not get expanded on. Just something that retcons parts of the series and says here's the twist.
You play through a series of rehashed episodes in chapter 2, but a great episode 43. You're excited to see what's going to happen in chapter 2. You get a chapter called the Truth. One altered cutscene at the beginning, new cutscenes at the end. That's it. No build up, no proper final boss fight. I had to check the internet to make sure I really did beat the game. Even worse, this mission featured all the tutorials in the "final" mission of the game. Every other MGS ends with this epic boss fight to celebrate the game and series, this ends with a same tutorial you played 50 hours ago.
Venom Snake being a near silent protagonist. I get that he's you, but it really hurt the narrative. If you're not going to show Venom as a character after the twist, at least give him more dialogue so we can see him as his own thing. The little dialogue he has is actually really great. The whole mission with the strain and you killing off your soldiers along with the ashes scene, I liked it. We got to really see Venom. Instead, we ended up with a lot of moments where you expected Venom to speak. In the entire game, Venom spoke to Skull Face once.
Real Big Boss was underutilized (along with the twist). I would've liked to have seen the descent into madness by at least one of them, but we got none of that. Medic seemed like a pretty chill guy. Big Boss's only descent was making Medic lose his identity and pass exactly like what happened to Skull Face (this is actually pretty cool) and leaving Kaz. I don't see any of the events explaining why they are the way they are for MG1 and 2. It's one of the things a lot of us wanted answered.
The retconning with explanations. Parasites are the new Nanomachines for the series. Having the need to explain the powers of Cobra Unit and such was really unnecessary. The whole story of parasites on a scientific level just didn't work for me. The whole ethnic cleansing with it was an interesting angle though. They also retconned the organization's name from Patriots to Cipher. The name for Patriots was already established in past MGS canon, but now they designated Patriots only for the AI that Sigint works on.
Last but not least, Episode 45. You permanently lose Quiet after this ending. The ending is actually really good and touching, but not being able to use Quiet as a buddy anymore was a terrible idea. MGSV only allows one save file, so you're stuck with having her gone after you trigger the events where Quiet leaves.