Assuming FO4 will be made by Beth itself, not by Obsidian or any other:
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1. I want a reason to go to most places, just like in Skyrim. There a lot of caves and other places in which I never sticked my nose, because that's what a person does in real life: don't go where you weren't invited/sent to. But most places had a task, even if small, like "kill the giant at X place", "find the X item in Y ruins", "rescue Rorik from Shimmermist Cave", "escort Rorik to Rorikstead" etc.
Sure, I don't need a reason to stop by an Imperial camp other then "Damn, it's midnight and raining, but there's an imperial camp over that hill, better ask to stay with them tonight".
But I won't get into a cave just because the compass shows it (my character himself probably didin't even see it). Hell, even if pass very close to it, add it to the map and Faendal says "A cave, think we should check it out?", I won't get in.
TL;DR - I want a quest or an entry jornal for at least 70% of the places in the game. I don't want, like in Fallout 3, to be sent across the game world just so I can find places by chance. My character is not necessarily the explorer you, developer, wants it to be. Besides, this is Fallout, a lawless wasteland with few survivors who avoid trouble, not TES, a fantasy world full of adventurers looking for gold and glory.
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2. Hunting, chopping wood (should have been more usefull, like in arrow crafting, firecamping, etc), mining and smithing feels nice in Skyrim. But it doesn't mean it will work great in FO4 in exactly the same way. Think and adapt as needed, don't just copy paste from one game to the other.
Also, the food & cook system really needs a change. In Skyrim, there is ZERO reason to eat and drink, since the character regens so fast out of combat, and has plenty of spells/potions to heal during combat. I never eat to heal, since healing with spells is so easy, lenty and also improves my restoration skill. In Fallout, we are all masters of stimpak hoarding, so no comments there too.
Resting, food and water should be use to restore some other status, maybe a separate condition/health (not hp)/whatever bar. The character would lose fixed amont of points in this "condition bar" at regular intervals to represent hunger, thirst and sleep deprival, with some penalties like "can't run", "aim tremble", "can't fast travel", etc, and finally die if the bar is depleted.
Hit points themselves could only be restores by stims (the have always been instant heal, I don't like this slow regen idea that came in New Vegas Hardcore mode), first aid, doctors and MAYBE stuff like the powder made with plants in FO2 (it would be like a very limited alchemy system).
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3. Efficient 3rd person combat, like in Skyrim (it feels way more efficient than in FO3/NV). A centralised camera is MUCH MUCH better then over the should, imo. Perhaps a cover system, bite me all Gear of War haters.
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4. Fewer town-style places, a lot farther from each other, no places like Bigtown (Arefu was the very limit of little population in an unsustainable place) and DEFINITELY no places like Canterbury Commons (the tradin hub of the Capital Wasteland had LESS people in it than Arefu? .|..).
I don't know how Oblivion was, but Skyrim, in my eyes, was a revolution in comparison to FO3. Feels good to see that it takes a while to ride from Riverwood to Whiterun, and from there to Rorikstead, Ivarstead or Windhelm; feels even better to find that these places are alive and well, if if sometimes too small (Rorikstead...).
I know in Fallout things can't be always well, in order to stay gritty, but none would be crazy enough to live of nothing in Bigtown, when they could just try the nearby Arefu (that bridge is big enough for a few more tents, and feels a lot more defendable) or Megaton (even if denied due to "lack of space", camping outside the walls like people did outside Vault City seems a better idea than Bigtown, much more after super mutant canibals become an iminent threat).
I won't even comment on Canterbury, that was an the very concept of insult.