I can't remember multitile citybuildings ever being denied. It's just that nobody with the skills had the time and put in the effort.
Personally, I have two issues with your suggestion already.
Say I have 1*2 buildings and 2*2 buildings. With my 1*2 buildings, they are designed to face the road on the short end. If I were to use your example grid, I would only want it to spawn horizontally, not vertically. However, I cannot remove the lower two "p", since otherwise 2x2 buildings could not spawn. Same is true for larger buildings, though 3*3 is probably as far as anyone should go anyway.
Perhaps a differentiation would help. Such that, say, if it's four "P", this specific cityrule only applies to 2*2 buildings, but if it's four "p", it would apply to any kind of building that would fit in. With mix&match (obviously, if you stay with your "top left" idea, the top left would always be P) As such, you would do
sssss
ts...
tsPP.
.spp.
.s...
And it would only apply to horizontal 1*2 or 2*2. Or some weird-shaped 3-tile-buildings (this approach does not forbid them, and factories or curiosities can have weird shapes, so why not?)
My second issue is more of a question - how would you go about building levels? First of all - if a 2*2 had the same level as a 1*1, would it have the same amount of pak, the same amount of pax/tile (like cur - act as individual buildings) or four times the amount of the 1*1 (same as before, but having any part in station coverage counts)
If you have an empty spot surrounden by highrise, and a new building would appear on that empty spot, but instead, it becomes a multitile building - how will the levels of other buildings affect the level of the new building? Generally speaking, one would not tear down a skyscraper unless the new building is at least as high/offers as much space. So the new building would need to be equal to the old one.