It actually shouldn't be THAT hard - the game has to assume you're not using Rank 4 Gunslinger, for example... and it cannot assume you are using Rifleman rank 4.... so if you have ~neither~ of those, you still have to be able to "win" the game. And the game can't assume you can lockpick or hack at all... in those cases where the story requires it, there is usually an NPC that can unlock the door, or there's another way around the problem (talk to an NPC to get the key, etc). Most perks just augment things you can already do.
The only problem would be those few that let you do things you ~cannot~ do without the perk. Like, without Local Leader, your settlements just would not be well developed at all. Locks would remain locked and computers would remain un-hacked (unless Companions do it, etc). You would not be able to breathe underwater for long periods without Aqua-Girl (but then, they cannot assume you have that one perk, so there has to be a way around that).