Some buildings will never be enterable because of possible references to terrorism and sensible situations (especially large public places like supermarkets or where a huge mass of people comes together). That could be solved due not being able to use "weapons" when you enter a particular location, but what's the point of adding it and taking efforts to construct an enterable location in a GTA what would be useless in the final game. Waste of efforts. Locations like schools, colleges, zoos, airports are never going to be enterable. Some locations like hospitals will lack some departments because of that too (and will be made quite simple if they are in (just like that one in GTA: IV). Don't expect a child hospital to be in the game.
But GTA V lacked elaborate interior locations that were in free-mode enterable (and not mission-only available). That's something that definitely needs to be better in the game. The GTA V world felt very empty because of lacking interior locations and because, the badly designed East Los Santos/working class-residential section (it was almost smaller than in GTA: SA) and of "the no point getting to the north"-problem. There should be more enterable locations in freemode. Everything we had in previous GTA's combined with new locations like more shops (and a variety of them, where you also actually can buy stuff and that you can rob (with a decent amount of money), casino/night clubs, outgoing areas (a huge diversity of bars/cafes/restaurants/dinners in varying price classes and varying style that attracts a different class in the population (rich, poor/ young vs old / both genders or mostly drunk men / nationality/culture (black/hispanic/white or irish/american/european/gang-related activity (gang bars)
What could be done too. More hotels/motels in both the city as the countryside where you can save the game as well in your room where you payed for. Most motels are very basic and you should save in no time (although enter the location, pay your room and than enter your room that is marked on the hub). But also luxury hotels where you can swim outside during daytime, 'meet' people, do different things in the hotel or eat a bit in the restaurant-section. A more elaborate vivid hotel but where the price amount is large.
A prison should be enterable as well. There is most likely only one prison in the game, so make it very well and comprehensive, and maybe focus one of your missions here (like rescuing a comrade or being locked in prison as yourself (and you need to escape). Make it difficult to escape, it could be one of the most beautifully made missions ever. A prison has a lot of potential. You could also make a fictional prison made in San Fierro based on Alcatraz (but still operating today).
NPC locations should definitely be enterable, and it should be done like they did it in GTA 5 with the protagonist locations. Random stuff is going on, and NPC's have lives too. If you visit them, they could be at home or they could be elsewhere. You can randomly encounter NPC's on the streets doing their usual business during the day. I'm of course referring to characters you will encounter in the game. If they are at home, you could enter their houses or ask to do an activity. Some NPC's have a family too and the way this should be implemented in the game should be the same as they did with the protagonists of GTA 5. That would be quite elaborate.
Should it be possible to enter houses of NPC's of characters you don't encounter in the game? I don't know. I think there should be a huge variety in interiors to make it fun enough and there would definitely be burglary missions in the game to do that. It could be fun, but i don't think it should be a priority. I'm more than happy enough if their gardens are already beautiful enough.