Characters with high repair AND the corresponding weapon skill should not only be able to build wieldable weapons (the arsenal of craftable weapons could be expanded via perks such as Mad Bomber - which would require an additional explosives skill) but also independent weapon systems like !BREAKING BAD SPOILER AHEAD! Walter White did in Season 5: https://www.youtube.com/watch?v=8Q8w8kkIL2A#t=1m
These would of course be uncontrollable once set, so players should be aware of that.
I prefer dynamite to remain local to the west (it helped the western flair of Vegas and I really liked the time bombs). So if you set your game at the east coast, give us alternative low level thrown explosives. MFC grenades and clusters were a very nice addition.
Good enemy and ally AI is absolutely necessary if you want dynamic and interesting combat. Enemies should use appropriate tools depending on the player's combat style, to defeat him. Reinstalling traps and mines is obligatory. If the pc makes use of power armor, intelligent foes should resort to EMP weapons (same goes for robotic companions).
Energy Weapons can be easily made distinct from Guns, the problem with that is that such weapons should be post-war creations or modifications to logically fit into the setting.
For example, all (half-automatic) Plasma weapons should be chargeable to introduce a new element of pace into combat. There could be a laser weapon that fires five independent bolts in a 30 degree cone in front of the user - of course this would nearly nullify the need to aim so it would have disadvantages in other areas. Or have it the other way around, chargeable laser weapons and a plasma weapon with cone shot. I'd prefer to only have one of the two types be chargeable.
Cut the optimized ammunition, it was only op and nothing else. Instead focus on something like hollow point and armor piercing ammunition, that is only useful in some situations and not any time. In fact with the new options added to Energy Weapons, I'd say cut alternative ammo for EWs altogether and instead focus on chargeable shots and other EW traits (like ammunition recycling).
Laser Weapons should have less spread than any other weapon type.
Have more enemies with high DT.
The Displacer Glove is a total joy, so it should return (of course balanced, like all weapons).
Certain Unarmed weapons (like power fist and its variants) should work on energy cells.
Shishkebab should return as a more balanced weapon that requires flamer fuel. Got no fuel, can still use shishkebab but without fire.
Poison should be reduced to three different versions (all useful in different situations, for different enemies) and also get corresponding perks to help making poison usage into a viable playstyle. Combine poison with thrown melee weapons and bladed weapons in general. No sledgehammer poisoning, as that don't make much sense.
Poison should be created as jars which have charges and can be used multiple times. They should require high survival to create (yes, NOT science, gameplay > realism) and be more efficient (in terms of crafting and charges, not in terms of damage) the higher your survival.
The primary crafting skills should be Repair (repairing would require time -> no use in combat! focus on Guns/Explosives ammunition along with Guns/Explosives, grenades and mines along with Explosives, weapon and armor modifications [along with the corresponding weapon skills], craftable weapons [along with -again- the corresponding weapon skills], repair kits -> no more weapon duplicate repair, only toolboxes with multiple charges like the poison jars -> Repair should be the most versatile crafting skill), Science (to craft chems and along with EWs energy weapon ammunition), Survival (food and poison, traps) and Medicine (medicine , like Stimpak variants and Doctor's bags).
So secondary crafting skills would be all weapon skills (useful only in combination with Repair and Science [only EW]).
Gimmicks like NV's gecko armors are also nice.
Traps could be created by the pc with enough Survival.
hardcoe mode should be default mode. So Survival doesn't need to come close to the healing capabilities of Medicine and instead focus on other areas.
A weapon that is in and of itself overpowered is not what the game needs. They all should revolve around certain playstyles and certain situations. A jack-of-all-trades weapon needs to be suboptimal in each and every occuring situation.
Camouflaged mines should be introduced. Also mine and trap detection should be dependent on the pc's Perception.
Camouflage itself (combination of survival and sneak skills) should be an option and also heavily used by enemies in the wilderness.
VATS needs to be a tactical tool, not a win button, that helps targeting enemy's weak spots. Disarmament should become a regular occurence.
If weapons have multiple uses, you can choose what to do with it in VATS (with varying AP costs). So the spinning wheel could for example be used to strike in melee (30 AP), but also to fire it's blade (50 AP)
Reintroduce first aid as a mechanic dependent on the pc's medicine skill and make it only useable outside of combat (as opposed to stimpaks).
Healing item and chem utilization should come with a short animation to prevent spamming and require thought to use them in combat. Healing should be over time.
Using items during combat should require AP.
Endurance should influence your sprinting time (ie the AP costs of sprinting), agility should influence your sprinting speed (along with what it does anyway, which is influencing the number of available AP). Enemies would also sprint of course.
THE MOST IMPORTANT THING: MORE SHORTCUTS! (poison dip shortcut, sprint shortcut of course, first aid shortcut, etc. it should feel as natural as the sneak button)
The one skill that I think is extremely hard to balance, make useful and interesting is Barter. Does anyone have good ideas what to do with it that Speech couldn't also do?
I mean creating perks that require a skill is one thing (god knows, Pack Rat was good), but the skill should have some worth itself.
Drastically reducing the amount of money is a start. Selling items with 1 Barter should bring in 1% of that item's worth. 100 Barter should bring 100%. Buying stuff would be very expensive with 1 Barter (increasing cost by 100%), while 100 Barter would let you buy the stuff for the original price.
Of course selling price would be less than buying price by default, even with high Barter.
Repair services should be overcosted without high Barter. With 100 Barter on the other hand, it would be very easy and viable to let your equipment be repaired.
So without Barter, the whole element of trade should be nearly outside of the player's reach (like locks are without Lockpick and speech checks without Speech).
This would not only empower Barter, but also the supplementary crafting skills (which lack the versatility and ease of trade of course) especially for crafting ammunition and medicine.
I also have a hard time imagining how to make weapon mods interesting. Moddable weapons should be fairly useless without mods to increase the mod's worth and make the subsequent choices more severe. There should be 3 mod slots and a higher number of available mods to introduce that choice. Enemies should use modded weapons with high frequency of course. It's not only for you. Their price would be fairly low consequently.