TPOSC SETTING UP A LOAD ORDER
( Your LO should be built around TPOSC )

Knowing it is pretty much 100% vanilla with all new units separate from the games and no changes to NPCs, or level list or new textures, but does place some 300 new NPCs into the world, not including enemy triggered-based spawns I would start my load order build for this mod like so.
I do not need to concern myself with towns, villages, or city mods. TPOSC does all that and alters the exteriors of cities and towns too. So forget Arthmoors CRF or PCS they are not compatible either. Including homes in and around Whiterun like Elysium without patch support. Have any doubts check the area in-game first! Or with xedit for conflicts.

I would start by loading my textures / graphical mods, water, and weather, for PC SKSE & SKYUI, ENB. 
I would set up my preferred lighting mods and the TPOSC patches to go with them if applicable. ( EL&FX / RLO )
The same for water and if I was using RW 2 and Alternate Start be sure to apply the TPOSC patches for those mods. 
I would ensure my patches are loaded as the author directed in the load order set-up. 

Just a heads up, if you are going to do a vanilla start then load TPOSC after the intro and after Helgen. Load the file, go to an interior and wait 48hrs this allows everything to reset. I suggest this as a precaution and as a sensible step, as a just-in-case really. I have found with many mods, not all, ones that add NPCs generally to the game, they seem to perform better after a period of 48hrs. So it seems logical to take this approach as a general rule. It seems to make a difference in my game over the years.

FOLLOW THIS LOAD ORDER ADVICE FOR TPOSC -- YOU SHOULD BUILD YOUR LOAD ORDER AROUND THIS MOD.

Quest Mods ( some exceptions to this - thinking of ESM-based quest mods.)
SMIM
Magic Mods
Grass Mods ( If you still get grass everywhere over other mod/settlements after altering your ini for values..use a different grass mod -this is why a grass mod is placed above settlements, etc. Verdant Not Compatible. I use The Elder Scrolls - Veydosebrom the old version and set grass settings to 80 or 90 which doesn't intrude upon my settlements. If you want to use other grass mods you may need to patch for them.  )
Weather Mods
Water Mods other than RW2 OR WATER FOR ENB
Creature Mods (Do not overload your game with too many spawning mods. TPOSC adds dragons - bandits and many new spawns to the game.)
Tree Mods-Skyrim 3D Trees
( textures and meshes changes are no issues. Mods that add lots of new trees to Skyrim are not, as I do this in this version. )
Town, city, Village Mods. ( This version edits all locations, and in most cases, exterior areas of the towns, cities & villages too. So another town, city, or village mods are NOT compatible. Or many outskirt mods of towns, cities, villages.)
NPC Mods / AI. ( Any follower mod should be fine unless it is quest base and adds navmesh or new locations in Skyrim. You would need to test.  Running multiple mods that add 100's of new NPC's and so on is not advisable. You will overload your game engine quite possibly. Immersive Citizens is not compatible.)
Alternate Start - Live Another life 
HD EMBERS  ( HD Embers works well with TPOSC. Some fire FX or lighting mods may need patches for the inns I have edited. A list of those inns edited is on the main description page under the summary.)
OR XD Embers ( Patch & info below )
MAGIC COLLEGE OF WINTERHOLD ( Magic College Of Winterhold can be used with TPOSC there is a small navmesh cross-over, however, I have tested in-game and checked in the CK and it seems to cause no issues. Gully NPC's path as they should and the MCOW seems not to be affected. I will patch should it be required.)
THE PEOPLE OF SKYRIM COMPLETE 
LUX / Lux Via Patch and load order information HERE
TPOSC Fishing Patch ( CC Content )  Patch and load order information HERE
XD Embers  - Patch and LO info HERE 
Riften Docks Overhaul - Patch and load order info HERE
EL&FX - Patch and load order information HERE
RLO - Patch and load order information HERE
TPOSC Falskaar Patch Patch can be found HERE
Skyrim 3D Trees tpos_S3Dtrees_patch.esp
Weathered Road Signs Fixed - Patch and load order information HERE
TPOSC Alt Start Patch - Patch can be found HERE ( This patch must be placed last in the LO after any other alt start patches that are used and most other patches too. Ensuring pathing stability in key areas.  )
WinterSun TPOSC Patch - Patch Can be found HERE Follow the load order
AiO collection of patches - Patch can be found HERE ( The AiO compatibility patch is for Lux, Lux Via, Orbis, Falskaar, Wyrmstooth, Beyond Skyrim - Wares of Tamriel SE, Alternate Start, JK's following mods, High Hrothgar, Temple Of Divines, Jorrvaskr, Dragons Reach, The Bannered Mare,  Belethors Goods, Warmaiden's, The Drunken Huntsman, Riverwood Trader, for The People Of Skyrim Complete. Other individual patches can be found here also.)
Water for ENB if used
Realistic Water 2
Patch For RW2 tposc_RW2_Patch.esp ( no longer required for RW 2 Version 5.3.0 or above )

NPC MODS ( If you get the black face bug for kids this is another mod altering the meshes. Contact that author for a patch. Some authors have already patched for this mod so check on their pages for a TPOSC patch. ) Or in some cases like Bijin NPCs SE you can try placing after TPOSC.

Optional:
RS CHILDREN PATCH

• UNDERSTAND THIS MOD BEFORE ADDING LOTS OF OTHER MODS
• DO NOT ADD CONTENT THAT ADDS NEW LOCATIONS WITHOUT CHECKING IN-GAME FIRST.
• DO NOT RUN MULTIPLE TYPES OF MODS THAT CONFLICT OR OVERLOAD YOUR ENGINE.
• DO NOT USE MODS THAT ADD NEW TREES TO THE GAME. TPOSC HAS NEW FORESTS.
• DO NOT PLACE ANY MOD BELOW TPOSC IN YOUR LO UNLESS IT IS A PATCH LIKE LAL OR IF I DIRECT YOU TO DO SO.
• DO NOT ADD MODS MID-GAME OR UNINSTALL.
• DO NOT THINK YOU CAN ADD ANY OTHER MOD EVEN A SMALL ONE TO ANY TOWN CITY OR VILLAGE WITHOUT CAUSING AN ERROR SOMEWHERE. IT IS HIGHLY UNLIKELY THAT YOU CAN.
• DO NOT RUN MULTIPLE MUSIC OR SOUND REPLACEMENTS OR ANY COMBO OF MODS THAT MIGHT STRESS OR UNDERMINE THE LO AND PERFORMANCE.
• DO NOT USE MULTIPLE SPAWN MODS OR ENEMY MODS - CHOOSE ONE IF YOU MUST TO ACCOMPANY TPOSC.
• SOME INTERIOR LIGHTING MODS WILL CLASH WITH TPOSC INNS AND WOULD NEED PATCHING.