First big problem I have with U4 is the pacing, which has been discussed at length. The other games had a much better feel for momentum, not dragging individual bits on for too long. There's a lot of focus on traversal in U4, but it's not engaging for long stretches. It's a particularly bad design decision to suddenly have an entire chapter dedicated to that (21) when you're deep in the finale of the game. That's one example, but there are more. I liked ch16 as a unit, but in the context of the game it was a bit poorly placed, coming right after an already slow chapter. I have no problem with less shoot-outs, but replace it with gameplay that's also engaging. The first half of the game is an even bigger offender. I actually enjoyed the second half more, which was more focused and felt like a long tribute to Drake's Fortune.
On the other hand, there's the tone of the story, which I felt was an even bigger miss. The approach closely resembled TLOU, and the mistake here was using this influence for a franchise that wasn't a perfect fit for it. TLOU had great introspective moments, but that fit the universe and the characters. The bond Ellie and Joel developed for example, was complexed and cut deeper than anything in the Uncharted universe. From the outset TLOU is way more character-driven, whereas Uncharted was kind of forced in this direction.
This is because Uncharted is -and should be- pure lighthearted pulp, with characters that weren't rounded or complex like Joel or Ellie were, which is fine. As much as I love Nate and Elena, I'm not that interested in their relationship therapy. I realized this when the optional convoys in the jeep/elevator chapter didn't do much for me. Don't get me wrong, I love them trying something new, but this was the wrong way to approach it. You can't inject mechanics that worked in TLOU, and expect them to work in a different franchise.
Combine these two points, and you get a game that tries to challenge what makes an Uncharted game (which I applaud), but ultimately fails at it. It was a gamble on two sides, and they lost both times.
Uncharted 4 showed that Hennig was just better at directing this franchise. I love what Drachmann did in TLOU (which is an understatement, it's one of my all time favorite games), but the experiments ultimately didn't pan out.