Plot Issues
1. Play out the sidequests anyway in the back burner
In a way this feels like a Shadowrun situation, and quite frankly if the players are chasing their own (maybe literal) ghosts, the factions are going to hire someone available to do it. Let the party handle their own stuff and a rival party gets the job. You can resolve the quest any way you feel appropriate for where the plot will develop, but now the players need to fight for their reputations. The next player plot hook could be buried in the rival groups.
2. Why not mix it up?
If the party is supposed to be a group of characters with high impact on their world, there is a way to make the character plots intercede with the core plots, even if they happen just a little off kilter from what you need to accomplish like the job is straightforward but Bob's old nemesis just can't see it go well, or George's scorned love demands a favor in exchange for forgiveness, or Nell's long lost sister might be in the mark faction's castle/town/whatever. While they may seem very divergent, the plot device has a setting for looping things together in the strangest of ways such that they all become related and keep the party together.
3. PC the NPC / NPC the PC
Do you have a specific way you want the quests to go? Follow one of the players on their sidequest (and anyone else with reason to be involved) and pre-gen NPCs for the rest of the characters to play - including a core enough personality to keep them involved. Meanwhile, the party does their quest. It might not be the smoothest accomplishment but it would then be up to you as the DM for embellishments but do reward the core party with the quest items for the players performing well in the side arc. This also gives you play room for fuzzy memory parts that you need to ad hoc or retcon.
4. Save this campaign for later
If the players are giving you enough plot to run a full game, it may mean that you should save this campaign for when you have a more attentive party - especially one where you can tell the players what they're in for to make characters in reaction to it. This is my least favorite idea but if they have these in depth characters that run parallel to the world you're running, it may be worth considering.
Motivation Issues
I'm hoping these are not the CN players who just enjoy what I call the Video Game Experience. To me, the Video Game Experience is that to the player, anything in the environment they can interact with needs to be important, monsters are just experience, and the plot itself doesn't necessarily need to matter if they get the levels and the loot. In this case they are almost turning themselves into NPCs if their actions really have nothing to do with the party.
It may be worthwhile to sit down with them to explain that these characters need a few tweaks to make the game harmonic. While a character can be selfish, the fact is that it's hard to run a full party with the truly self indulgent within it. Tell them that they can keep their characters, perhaps even as they are but the player becomes responsible at least up front with why the character is with the group. After encountering a situations where the characters don't mesh or the lone wolf amidst the team, DMs in my area have started telling people that even if they make characters on their own, it's up to them to make party cohesion work. Sometimes it doesn't matter and the DM holds the leash for some major plot hook, but the fact is that in the seemingly sandbox world you have, the party dynamic is player driven.
I would recommend using the Monster Vault maths, found summarized on Blog of Holding; or, Monster Maker is a handy app that helps create monster cards, and will work out the maths if desired.
Set out which roles you wish the monsters to take - from the sounds of things it seems like you'll have a mix of Lurkers and Skirmishers, with Soldiers and Brutes making up the majority of the rest. Adding some of the other roles (artillery and controller) will help build variety.
Essentially you will be making sets of 'monsters' to form into encounters. From memory approximately the same number of same-level enemies makes a relatively balanced encounter, depending on the level of optimization and experience of the players. Mix and match some monster types, replacing 1 monster with 4 minions of the same level, and nudge up or down to taste.
For example, for 5 level 1 PCs you could then have 2 'Tough Monks' (level 1 Soldiers), 2 Ninja (level 1 Lurker), 4 mook monks (level 1 skirmisher minions) and 4 ninja mooks (4 level 1 artillery minions).
The DMG 2 has a section on making monster 'themes' - in essence by putting together sets of additional abilities that are thematically linked - such as the Goblins' ability to shift. For instance, you could add an ability to the Monks that acts in a manner similar to the Monk PCs flurry of blows - maybe on a successful attack they deal a small amount of damage to an additional adjacent enemy, maybe 2 damage for a level 1 monster.
One of the easiest tricks for 4e is to simply 'reskin' a monster - presenting for example, a goblin or a kobold as a ninja is just a question of description. Find a monster which has the relevant ability (such as shifting on a miss, those pesky goblins!) and you're good to go.
Generally a 4e encounter is much better with some environmental factors, so I'd recommend adding in some interesting terrain features or traps to spice things up a little. Broadly speaking, avoid adding in higher level Soldiers or Brutes too much, because they can become hard to hit leading encounters to bog down. Lots of minions is useful in making an encounter feel exciting and allowing the PCs to feel capable heroes - it all comes down to description when using minions - you can make the heroes feel awesome or like they wasted their attack depending on how you invoke their sense of adventure.
The monks could have the ability to spread some splash damage as a flurry of blows, the ninja should be tricky to pin down, maybe with a teleport style ability or a jump. They could climb walls with normal movement for a more HK film feel. The tattoos sound like a great idea, possibly you could borrow from Legend of the 5 Rings and each style of tattoo grants an ability - so the monks with flame or dragon tattoos can breath fire. Monsters that spawn other monsters are fairly tough - the Wraith in 4e does something similar I think. Make sure that whatever comes afterwards can't spawn more monsters - maybe it generates a minion when killed that lacks the respawn ability. Alternatively, you could describe them as crumbling and rising once they hit Bloodied, with some new abilities?
Best Answer
So first of all, I really like this idea. I tried it once or twice a long time ago and I'm still fantasizing about it. With that out of the way, let's move to my 2 cents.
Make the NPCs well-rounded characters
These NPCs aren't just some recurring characters, not to mention some one-time ones. They're gonna be with the party for a very long time. Whole adventures, actually, which is quite a lot. This means that they should be really well rounded. Your players should get to the point of distinguishing between them after just a few words, especially when the NPCs are the ones who spark the conversation.
More than that, though, they should be more than cardstock characters. You want them to express feelings, you want them to have goals, and you want them to react. Otherwise, your players will have hard time connecting with them, and this is far less good. As a rule of thumb, make them round and distinguishable from each other. A wizard is different from a fighter, true, but we want a greater difference. The prince will have hard time adjusting to the wilderness and to the bugs in his bed. The merchant will always stop to collect the better loot so she'll be able to earn much from those bargains. Classes are a dirty way to distinguish, but they're better when accompanied by some other traits.
Don't let them speak right one after the other
The players aren't coming for the game as an audience for a theater, they're here to play, and hearing NPCs talk with each other is far less fun. If you must make them speak between themselves, make it as quickly as you can and immediately move on. If you can narrate the conversation instead ("they're talking about what happened, Elsa thinks that they should go east and Hans thinks that they should go west…"), it is far far better.
Give the players the center stage
The players and their characters are the real stars of the campaign. The NPCs are extras, and should always be seen like for you that when you're playing them. If they're far cooler than the PCs, or if they have much more screen time, something is off with your campaign. It's better to not have the NPCs with the group than to let them illuminate and shadow the PCs.
They're not all knowing
Think for yourself what is more important, a character who knows everything or a character who knows only part of them. For me, it is the latter. That comes from one simple thing: There's no drama when everyone knows everything (it is not entirely true, but that's for another time). Make them say sometimes stupid or idiotic things, make them come to wrong conclusions, let them make mistakes. They're not a kind of supernatural deity who knows everything, but humanoids who are as humane as the characters, and they should be played this way.
Make them important for the story
They should always be important to the overall story, in one way or another. In one of my more successful D&D campaigns, the characters had to escort a princess to a neighboring kingdom through the forests. Having to keep her safe from one hand, and dealing with all of her complaints from the other one made the game so much richer. They don't have to be important to each and every one of the scenes, but they should always be important for the overall story. Otherwise, the characters may just leave them to rot one day, when things will turn the wrong way.
And an end
Hope I succeeded with helping you a little bit.