I haven't had to deal with this scale of additional builds to an existing structure, but I would deal with it simply with a linked model (existing structure).

This allows you probably the best visual control, you can still link all your views from the original project or over-ride them as required.
It also means you can speed up working by simply turning off the linked file for a while if you don't really need it to complete the additions.
It also means that you can have complete independence from the original grids and levels.

Depending on size, you could do separate models for each addition but that will become a bit of a nightmare for linking at some point, but again allows you complete independence with grids and levels.

Its really hard to judge without seeing the project to make a judgement on it.
Is there a way to rationalize zones and grid layouts so that they comprise more than one addition? Then you could use worksets, or even phases (set each new build addition as a phase)..

There is kind of no wrong way to do it, just ways that will make your life easier or harder.

I generally try to split up models based on design teams, deadlines, sectors or levels...there are many things to take into consideration to split up models and me personally, I like to think about who is working on it also because I might have people working at distance and I can't put them on the same building as others that are local...complicated no doubt...

good luck

Using separate phases for each addition is absolutely the way to go. I've found this very helpful for questions that come up later in the project that relate to some element of the existing structure. You can quickly identify the phase of a given existing element and hence the correct as-built drawings associated with them (if you're lucky enough to have them).

I also agree that it's a good idea to maintain a "master model" linked into a separate sheet file, as you suggest, especially if you anticipate future projects on the same structure, which it sounds like you do. I've done work on projects like this with "master model" file sizes exceeding 250k, and it hasn't been an issue. One thing we make sure to do is set up plan views in the master model with visibility settings intended to be used in the sheet files. On these views we add live tags, dimensions, and anything that may be inadvertently deleted from the sheet model if the link is accidentally removed.

As far as worksets are concerned, I would just go with the typical rules - Workset 1, Shared Level & Grids, linked Arch, linked MEP, etc. In both the "master model" and sheet file, you will likely want to set up the project so that it opens with the window prompting the user to specify which worksets to open. This will save on the time it takes to load the file.