http://www.katties.se/images/2008/jack-russell-terrier_3156364.jpg
I think an optional turn-based system would be cool, like how you enter VATS and you aim for body parts (eyes and groin again, please! And for melee aswell!), and when you are done using up your AP attacking, it's the opponents turn to use his AP targeting your, or your companions, body parts. And then your companion targets some enemy's body parts for his AP... and so it goes. Would be coolest when there are many opponents. Always feel better coming out from a fight in turn-based versus three times more enemies than it does in FPS because then you don't have to worry about if you've put skill points in the right skills, and any perks that enhance AP, AC and whatever, and that your character is better than the enemy characters. In an FPS you just need to worry about having a good weapon, and your own aiming skill.
I also think a node system would be cool. It would make the game world feel sooo much bigger if you could travel across states! I mean, Fallout 1, 2 and Tactics cover states! Fallout 3 and NV just cover a part of a city and the surrounding area. I think it would be cool if you could choose to walk through the wasteland (wasteland would actually be a wasteland, a nothingness, just unfertile earth, ruins and junk under the hot sun or raging storm) between the "points of interest", the nodes, which would be... well, settlements and the surrounding areas that may have anything interesting, but also, you know, caves and buildings/towns worth lootable, and quest locations, and faction HQ's... such things. There could of course be as much, if not more, "points of interest" (that is, playable area with something interesting, like, say, the world map of Fallout 3) than in Fallout 3 or Fallout NV.
Also, the implemention of different vehicles and mounts would help with travelling these distances. Having a horse, a donkey, a brahmin, a giant mole rat, a jeep, a motorcycle with a cart, a truck, or a custom-built vehicle (or a Chrysalis Motors Highwayman!) would speed up travelling, and also make it more funny in real time (well, not maybe riding a donkey or brahmin across a wasteland and town ruins) and you'd also be able to bring a lot more stuff, and some companions.
Edit: On the topic of distances between places in Fallout 3 for example. I thought it felt pretty stupid when... that blonde chick in Megaton... hands me a letter for me to deliver to her parents in Arefu, and she doesn't go herself because it's dangerous and whatnot. When she said it, she made it feel like it was a long way there, to some settlement, like in Fallout 2 when they say "That town lies south of here, a three days journey" or something. But they way to Arefu was only... a little walk away, it felt.
this is starting to sound like it should be in the speculations and suggestions thread.
but i had to respond...
as i'm sure you know, i'm not down for nodes, and the fact is it's highly unlikely to happen. but there is a great compromise here that works basically the same - especially with the intro of vehicles, which i also would love, and is a likely addition. basically just take the sandbox system they already have, but add in large amounts of wasteland, huge tracts of basically empty map - easy to design, shouldn't take up that much more processing power or memory, and adds a massive scope to the world, as well as a great new gameplay element in vehicles, PLUS it allows for a greater variety in the world - you can have really harsh, inhospitable areas, sort of moderate but still terrible areas, as well as some small areas where maybe some life is starting to come back. its basically what you want, just in the context of an open map, which to me feels much more fluid and dynamic, and much more realistic, which is where they're trying to take the series - immersive. i mean come one they're basically jiving off mad max anyway, why not take it all the way?
and as for TBC, F@!% that. FPS is so much more visceral, dynamic, exciting, and just plain cool - also, again, highly unlikely to happen. basically, it's not gonna, and probably you know that just as well as i do. i say just make the FPS elements work better, by adding some kind of cover system and some better AI, and creating a quick lock through the iron sighting, just like Call of Duty has - as long as you're pointing in the direction of an NPC, popping on the iron sight will quickly snap your aim to the target - releasing and pressing again will snap to another potential target. its not a gimme that completely reduces gameplay difficulty, but its a little something to make combat feel a little more fluid and dynamic. its telling that you said "always fell better comin OUT of combat" ... what about how you feel when you're in combat? with TBC, you don't really wind up feeling like you're in combat at all.
I'd go so far as to saying that I'd like to see VATS become more like a "bullet-time" type thing, to make it more in line with the real-time combat of the rest of the game. i always found it wierd that there was this pause menu thing where i could just select actions and then watch them play out... whack if you ask me. once again, IMMERSIVE. make me feel like i'm there - that's what Bethesda is working towards, and that's what I and the majority of the fanbase want to see. also if its greater combat strategy and increased importance of character builds you want to see, that's exactly what I'd like as well, but there are ways to do that within the existing framework. you're not getting TBC and you know it. so why not think of ways to make FPS more strategic (cover system is one - different types of enemies with a lot of different strategies necessary to take them out is another (and better AI)) rather than asking for stuff you know isn't gonna happen.