Early in the game, irrigating grasslands doesn't help at all because Despotism removes that extra food. Later, if you have an all-grassland city, with irrigated grasslands, it will grow quicker than you can build the hospital, so for a long time all that extra food will be wasted. Even later you'll only need population size 20 to work all squares in the city radius. Everything above contributes to population score (and money or science if you use taxmen/scientists) but not much more. I find it more fun to have 80+ shield output per turn (20 mined grasslands with railroads, factory, powerplant etc.) than to get a 21+ population and higher score.
If you have mixed terrain, in particular hills and mountains, you'll need to irrigate some of the grasslands to work these other sqares. But that's the most I ever irrigate -- although you may find a quick-growing city good for worker and settler output.
Other than that, I noticed that the AI doesn't seem to build productive cities, and automated workers look at each single square, which is useless. I don't need to mine mountain squares if I don't have any 3+ food squares in the city radius. Similarly mining all desert sqares around an all-desert city doesn't make sense, since I cannot support the population to work them. However a city completely in the desert, with all squares irrigated and railroaded, can grow big and fairly productive (20 squares with one shield and two food each).
So don't look at the isolated squares, look at everything that's in the city radius.