I believe that almost everyone will agree with me when I say that Skyrim's radiant quests were unsatisfying at best, and they need to be reworked a bit. And, that said, handcrafted quests are necessary for literally 98% of game content.
However, I do believe that there's still a place for radiant quests, but they require a radical redesign, and change of Bethesda's approach towards them. I will elaborate.
In Skyrim, the radiant quests basically amounted to 'Follow Marker to Location. Kill/Take/Steal randomized Person/Thing. Return for Minor Reward.' It's a very simplistic formula, and offers an experience which the word 'generic' and 'uninspired' only begins to describe. Now I can't blame Bethesda, this being their first real foray into radiant questing it gave them an easy way to say 'our game has unlimited quests' and add some meat (albeit stringy and tasteless meat) to a game that was already a little shallow when it came to faction interactions and quests.
In Fallout 4 we need a system where the game features only a small amount of radiant quests - between three and five at launch, say. But each radiant quest would be fairly elaborate, and feature a large amount of handcrafted elements and thought put into them such that they are more of an 'event', and less of a 'chore'. The old formula would be done away with, and instead each radiant quest is an interesting situation, which randomly branches into different directions.
For example. Let's say there's a radiant quest that involves escorting a caravan of traders or settlers.
1. Caravan departs from random place to random destination. It moves quickly so the player isn't loitering around thinking 'God, hurry the frack up...' Possibly it is motorized, for example a flatbed truck where the player rides in the back.
2. Event
2a. Caravan is attacked by men on motorcycles, and the player must shoot them from back of moving vehicle while caravan tries to escape.
2b. Caravan runs into a road block set up by raiders. The player can either bribe the raiders to let them through, paying a toll. He can fight his way through. Or he take other decisions
2c. Caravan breaks down and must be defended in a short battle.
2d. Caravan guards have been bribed to switch sides and help raiders in combination with one of the above.
3. Caravan arrives safely. Player gets rewarded randomly, but often with more than just a small amount of money - chance for a rare weapon, for example.
Another example. A quest involving bounty hunting.
1. Obtain quest to hunt a randomly generated character with a randomly generated name and small backstory. One of, say, 20 each...Todd told us they'd recorded 1,000+ common names to be used for the baby, why not record 20-30 names for randomly generated bad guys?
2. Hunt for bad guy.
2a. Find his hideout, and get ambushed.
2b. Go a town and find a family member/associate of his, trying to persuade them to give him up. May lead to finding him asleep, or drunk in a tavern and vulnerable, letting you bring him in alive for extra reward.
2c. Find his hideout, have an opportunity to talk him into surrendering peacefully.
2d. Have the bad guy offer you a reward for helping him fake his death. Or find out that he's not the bad guy afterall, opening up a quest to help him clear his name.
2e. You find the badguy in a public place, where he takes a hostage which puts karma and possibly rewards at stake if you can't save the hostage now.
2f. Bad guy finds you and tries to take you while you're sleeping, only possible if you've been on a bounty quest for awhile and have been ignoring it.
3. Reward.
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So the key is to make radiant quests that have enough branches and possibilities that you may need to do it five or six times before you even realize it's being randomly generated. This necessitates a large amount of dialogue, and possibly variations of that dialogue recorded to give even the same, or similar situations, a different feel to it. It's late so I won't type much more and most people probably won't read what I've already typed.
If you want to make radiant quests a worthy addition to the game, you must put a lot of effort into them, rather than kind of using them as a tacked on way to bump up the quest amount. So, if Bethesda decided to focus on only three to five radiant quest-lines, and flesh them all out with maybe six or so different paths and outcomes each, and make them more elaborate, I think they would be more engaging and more worth bothering with.