You run FR, yes? I'm pretty well versed in the source material so if you give me (a) the factions/organizations you're thinking of running and (b) the timeline/gist of where your game is grounded, it would focus my thoughts and I could probably give you a decent go at how to actualize:
My Loudwater campaign -
http://frloudwater.blogspot.co.uk/
Been running for two years, so quite a lot of stuff...
Currently active evil factions include the Darkhold Zhentarim (who are building a fort in the Southwood around an old Ammarindar Portal), the Serpent Realm of Najara (who had been seizing women for nefarious purposes), various Banite groups - the evil dwarf Mountain King Oro Loroth on the River Loagrann, the Banites under Kitana serving Queen Esmerelda of Llorkh, and remnants of the Hand of Naarash cult under Dajani the Tiefling on the Upper Delimbiyr. The Southwood goblins are a minor faction, not really a big threat unless you invade their fortress of Korzzbad. The Severed Eye Orcs are in Bleached Bones pass.
The Ashmadai cult in Waterdeep have been mentioned, and Netheril is waiting in the wings, having taken Spellgard, with Thay further afield. I have a 30-year sketch of how the Netheril/Thay conflict may play out and involve the PCs in the high Paragon through Epic tiers.
Good factions include Loudwater under Lady Moonfire, the Light of the Sun Amaunator paladins & clerics allied with Queen Valeris of Orlbar (who is Unaligned), the wood elves south of the Star Mounts (Graywood Elves), the Glintshield dwarves in Bleached Bones Pass, and further afield King Pyvim Kyatt, the new secular ruler of Elturgard, who has pledged to cleanse the Reaching Wood of gnolls after a raid on Scornubel killed hundreds, ousted the old High Observer, and brought him to power. Luruar is a long way off beyond the High Forest and currently not really active, but could become involved.
Unaligned but generally benevolent factions include Queen Valeris, an adventuress who drove the Banites from Orlbar, the Duchy of Daggerford under Duke Haskar Tyndal, Waterdeep, which is focused on rebuilding Neverwinter, and Baldur's Gate (inactive). Daggerford is mostly concerned with staying independent of Waterdeep and controlling trade up the Grayflow.
I'll be running P2 Demon Queen's Enclave about an Orcus exarch's undead incursion against a drow enclave Phaervorul (established by Erylyndn IMC) in the Underdark near the Endless Caverns. Probably run Against the Giants after that, with a three pronged Giant & Orc invasion of the Vale, then the Thay/Netheril conflict will escalate in the Epic Tier. PCs may ally with Netheril vs Szass Tam, or not. I'm thinking Szass Tam as an undead guy may ally with Orcus rather than Bane, which would make P2 useful foreshadowing; not sure about that though.