For me it's being bored. I know it sounds like some general answer, but still.
I've been gaming since I was 2, and of course I get bored time to time with it, but it is significantly harder than in real life.

For various reasons, the primary means of transportation in my country is Motorcycle.

But I never experience an open-world game that really capture how people who used them daily irl. From Vice City, Sleeping Dogs and now even in Cyberpunk2077, It's always a clunky and awkward experience, making a motorcycle only as an alternative.

You can't make an spit-second turn in an instant
You can't speed up and squeeze your bike in a body-width narrow space
When you need to turn around the manual reverse is slow and tedious
The turn radius in high speed is never optimal
You can't maximize the storing capacity in them

Collaborate and think laterally.

In real life, it's trivial to grab a scrap of paper and a pen and draw a diagram, or gesture in three dimensions, take a stick and draw in the sand, or stack up some clutter to make a model, or any other collaborative technique you need. In a computer/video game, the best you're likely to get is voice chat and maybe a webcam window.

Likewise, the order is still "real life, then ad-hoc play, then pen-and-paper games, then computer/video games" for allowing you to come up with out-of-the-box solutions to problems, and to make your own gameplay variants. If I can ever get my more important non-game projects done, I'd love to try to make an urban multiplayer deathmatch game with elements of GTA 2 and 3 and a big emphasis on constructing and customizing your own weapons and traps using found materials.

...not that it's surprising. The history of games is all about finding ways to come up with simplified versions of reality, either to keep things fast-paced or to work within hardware limitations.

Drive. In almost every game I've played that isn't a dedicated racing game (and even some of those), it feels like when you drive in games you go flying into a wall or take out 3 pedestrians if you so much as tap the accelerator or the steering wheel.

Use a simple tool like a crowbar or hammer whilst "surviving" without its quality degrading into nothing after 10x uses like it's made of cardboard instead of steel...

Unless the game uses a first-person camera, seeing what your character can see may be an issue. For example, in the original Super Mario RPG there's an NPC you can talk to but never see, because he's standing behind a building (so you can't see Mario at this point either). For years it was speculated that this was meant to be Luigi. As I recall, when someone removed the foreground tiles via an emulator, it turned out the NPC had no sprite assigned.

Moving any liquid from one container to another, we still don't have widespread technology for it.

Climbing fences. Easy in life. In games, they're just impassable walls.

Surviving dreams. Sometimes you have to fight dream daemons in games during dreams.

Carrying items near walls or near other objects is practically impossible in a video game and if it behaved in a similar way in real life you'd just break your own legs and arms by attempting such a drastic stunt.

Similarly, carrying any kind of open box that has smaller objects inside it usually just results in a rain of tiny objects coming out of the box in a game.

I'd say it would be my favourite activity, swimming. Try to swim in a game? Maybe it's lava, or you can't interact with it, or you get lucky and you actually can swim! Only to be tired of holding on to the forward button and/or bored of the scenery and wish you can do something to gets you about faster.

Some days it sure seems like we want our games to be fast but our lives to be slow, huh.

Since it doesn't say we're limited to one thing, I'll list several.

1. It's HARDER to "feel" things in a game, the way we can "feel" real life when it comes to our senses. It's still enjoyable, just limited to our sense of sight and hearing for now. (Haven't tried VR. so, can't comment on that) Then again, we don't have to "feel" pain in a game either. Just thinking of some of those max gore settings in games (/shudders).

2. When it comes to RTS games, it's HARDER to "think" as fast as the AI I play against, so I'm a lot slower to plan my responses vs the computer AI player(s). Thank goodness for the pause feature in most RTS. Granted that real life doesn't have a pause feature either, wouldn't that be something.

3. Most platformer games (Volgarr the Viking, I'm looking at you!), it's so much HARDER to get my fingers to "react" to the incredibly fast paced action, even if my mind is capable. Then again, I don't have to carry a sword in real life constantly defending myself from respawning enemies.

4. It's HARDER to "yell" at a computer game when things get frustrating, especially when a nasty bug crashes your game and you forgot to save for the past hour. The game simply doesn't care about your feelings lol. Real life doesn't share that problem...not that I go around yelling at people every time I get frustrated. WHAT KIND OF PERSON DO YOU TAKE ME FOR!!! Oops…ahem, yes, well, where was I...

5. I'm going to leave it at that for now, I may add more later. I got an anime to watch and I'm late for it. :)

The Saint's Magic Power Is Omnipotent, here I come!
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Running- In many games with RPG mechanics, in order to accommodate a sense of progression, the initial speed/duration of the player's running/sprinting capability is abysmal. Morrowind comes to mind.

Picking up objects - In most games the simple act of picking up or carrying objects in hand is a clunky experience.

Live a normal life - By design most game narratives strive for a unusual / singular life(path) for its protagonist(s). So this makes it harder to engage in ordinary mundane activities of life. Most games, even if they include some ordinary actions i.e. using wash basin, would render everyday actions devoid of any consequence.

Traversing Sewer systems - No monsters in real life, I guess. :)

Finding objects - In Hidden Object Games.

Speaking with other people - In most games one can only interact with other characters based on a set of preordained verbal and interactional responses. So communication in games is harder compared to real life.


Can we add more points later?

Use a RC Helicopter/airplane i am sure that is fun in real life but in gta is just hell

The hardest thing to do is pause. I can pause my game and be good. But I can't pause life. It just keeps rolling