I also like to make giant cities, but there is a serious case of diminishing returns going on here. My claim is that the same amount of population in several smaller cities outperform a giant city, and not just by a small amount. So let's do the comparison, and see how the size 42 city you mentioned would compare to 4 cities of sizes 11, 11, 10 and 10.
Worked tiles
With the same number of citizens, the smaller cities can work as many tiles as the giant one...except, there are not 42 workable tiles within the three hex range. The maximum is 36, from which you would have to subtract all the non-workable tiles, such as Mountains, Wonders and several districts which don't have specialist slots. Then there's the quality of the tiles. The smaller cities will be working their 10-11 best tiles, the giant city does not get to choose, and will be working many weak tiles.
Smaller cities win.
Districts
If my math is correct, a size 42 city has 14 district slots. It will not be able to use all of these, as there are not that many districts in the game which counts towards that limit, and you can only have one district of each type.
The smaller cities in this case has 16 district slots, all of which can be used for useful districts. You can have up to four of each district type, meaning you are free to prioritize what is most beneficial. You would typically have four Campuses, each city would have a Commercial Hub or Harbour, and so on.
There also isn't any great synergies to be had from having more districts within the same city. There are minor adjacencies for most districts. The main synergies are between the Industrial Zone and the green districts, but those don't count towards the district cap, so the smaller cities outperform the giant one in that regard as well. Smaller cities can also put their districts in the same area to benefit from district adjacencies, and even do things like putting an Industrial Zone next to 2 Aqueducts and a Dam. The smaller cities will also have access to better district spots in general, as they cover a much greater area.
Smaller cities win.
Trade routes
1 city gets 1 trade route, 4 cities get 4 trade routes.
Smaller cities win.
Great people
Tied to districts and district buildings, of which the smaller cities get more, and with more flexibility.
Smaller cities win.
Wonders
The giant city will be able to build wonders a bit quicker. However, the smaller cities have a lot more space available, will satisfy more placement restrictions, and their combined production will be much greater.
Smaller cities win.
Specialists
Specialists are not great in Civ 6, but for what it is worth, the smaller cities can have more slots, and if they wanted to, could have more specialists. The only reason why the giant city might be using more specialists, is that it has no better use for its citizens.
Smaller cities win.
Tourism
As has been pointed out, you don't need to work tourism tiles. I would also point out that the smaller cities will have more of both space and high appeal tiles for Seaside Resorts and National Parks.
Smaller cities win.
City Projects
The smaller cities have a higher combined production, and as such, will be able to run more projects.
Smaller cities win.
I think the picture is pretty clear, tall cities just get you a lot less per population. I can only really think of three things for which a giant city is useful:
- Pingala, he can grant a single city the ability to produce a significant amount of science and culture, based on population
- Concentrated production for one-off space race projects
- Concentrated loyalty pressure
I don't think these are sufficient to say that tall cities are anywhere near competitive to smaller ones (per population).