Even if you have several way to unlock the chest, or even if the chest was not locked, it boil down to how much you do it, how much time you spend doing it in the whole game compared with how much time you spend doing other stuff. If 50% of your whole playthrough is about lockpicking, there is a huge problem with the game. You doing some kind of grind/job/chore instead of enjoying the gameworld. But the lockpicking stuff is just one of those issues.
Genericness takes the cake the most, IMO. I take two post-apocalyptic FPS. In Metro 2033/Metro Last Light, you spend like 30% of the game learning about the lore, interacting with characters, 30% gearing up, walking in the dark wondering about when the monsters will attack and 30% fighting like a classic FPS. (more or less). The FPS parts aren't the majority of the game (at least how i see it), they have some time between them, they are always differents (different environnement, enemies, context), and your behavior is always different. Sometimes you shoot, sometime you hide, sometime you have to look the opponement into the eyes to make them leave, sometimes you just have to use the light. It always keep things fresh, let you ask more.
On the other hand, Fallout 3 is a much longer game, that involve far much combats in a IP that was never about fight, but post-nuclear societies. A good half of the game "content" is made of abandoned metro full of hostiles ghouls and abandoned DC urban areas, full of hostiles super-mutants. Not only it disrespect ghouls/super-Mutants, make you shoot those factions as only interraction, but you end up in a whole lot of areas in which you do the same things over and over. You shoot the same faces, you "explore" the same copy-pasted areas, you loot the same randomized shelved for dozen of hours. It is clearly a case of artificially extended lenght, that would only make you bored with the game. And when the (lame) interactive content finally appear, you are not as much into it, as you consider that you wasted too much time to reach it. And when the next abandoned metro appears... You just wonder if it is worthy to go through that again for the next piece of content, or if you should just log off and forget about that game.
Then when reaching FoNV, the "pieces" of contents are far more than pieces and are much, much more interesting, the in-between are less generic, but you still have to walk in empty places, face generic critters, loot the same random shelves, and other stuff. Sure, the content is better, but the "work" you have to do before reaching the content is still pretty repetitive/boring/un-involving. You just mindlessly go through it, while think about what could happen next. When the number of filler is low, you could go through it without minding. If it represent 50% or more of the games, you feel like all what you did was filler. And if that generic filler is less than 50% but the games takes hundreds of hours, those less than 50% could become still an high number.
In short, i would say that a short game can make those filler be forgiven, but the longer the game become, the more the filler parts become hard to sustain.
So it is something about
(Time spent with fillers/Time spent with unique contents)* Overall Lenght = Chances of quit the game before the end
(you still can defy the stats and end up finishing a game that you have 99% chances to quit before the end)
We are talking about games that deliver unique contents.
Some games are just about repetition, but those are what the players are looking for. When you play Tetris, you know you will do the same thing over and over.
You aren't tricked into tedious task while expecting to interact with that world or feel a well done atmosphere.