So you want my recommendations huh? Well, I say 200-250 total, 300 at the most for the full regional Dex. My region of Zantaru currently has 256 Pokémon in it, including Mythicals, and won't have many more. 303 like BW2 and SM is a bit much, and XY's 453 is ridiculous. 250 is a nice amount and you can get a lot done, my region has ~160 fake Pokémon and still has room for some original mons too. Really it depends on the size of your game's region - if you have many routes or bigger routes, like Sun and Moon, then maybe a Dex of 300ish makes sense. If you have a smaller region, like Kanto pre-GSCHGSS or Sinnoh, then maybe even a Dex of 250 seems large, let alone Kalos (the smallest region physically and additions-of-Pokémon-ly, how ironic)'s 450.
And you're concerned about leaving some of your favorite mons out? Don't be, it SHOULD BE THAT WAY. In fact, it almost NEEDS to be that way. You WANT to leave some of your favorite mons out - if you like them, chances are a lot of others will too. People should be forced out of their comfort zone and be forced to pick Pokémon they don't know about or necessarily like - if you really want all your favorites, you might as well add all 802 Pokémon from Bulbasaur to Marshadow like my friend Alex. Though in his game, the POINT is that they all exist, but whatever. If you want to use them in playtesting, that's what debug mode's for, amirite? Proper playtesting should be played like the game would by a non-dev, but still.
Amount of Pokémon per route, huh? Well, longer routes you can get away with more, but typically I try to have four Pokémon per route per encounter method, maybe five. And introducing only one or two most of the time would be good, particularly for the early routes. Two or three for fishing/surfing on the routes that have them, and if you do, almost NO variation across the region, because you don't have time for that. And the Pokémon on a route usually should fit a theme, like how in Zantaru, one of my routes is devoted to Fairy-type Pokémon. And that's true even with longer routes that may have six or even seven Pokémon on them, and in fact the aforementioned Fairy-type route has three different Fairy-type evolutionary lines accounted for, and Eevee and a couple others on top of it, just in a map section of tall grass, despite Route 14 being one of the longest routes in the game. It could get away with having ten or eleven lines in just the tall grass, like Kalos, but doesn't because why would it? Longer routes can have more per encounter method by splitting the route into multiple parts, like literally every single area of Sun and Moon does. It doesn't even have to be through a transition or something - Alola's Route 1, I think the longest route outside of Vast Poni Canyon, the one that never ends, has about four different tall grass encounter sets, and yet no transitions are present, or anything else to indicate a change in encounters. Just have a RPGMXP map break or something, it's alright.
A region of about 25 routes of an average of medium size, like Zantaru, should be able to house between 200 and 250 Pokémon easily, even with only three to seven lines per route. My suggestion is, assume each route has 15 Pokémon of the Dex accounted for. Multiply by the amount of routes, and you get the maximum size of the regional Dex. Then, put about five lines per route and you should be good to go! My route-based biggest advice is NOT to take Santalune Forest's nine lines and like, 25 Pokémon as an indication of your routes by ANY means whatsoever. Happy gamemaking!
-Alexherobrine45/SuperLunala