You can do a lot with Twine (and the Sugarcube story format).
I learned it using this Youtube tutorial series.
So having moved from RAGS to Twine 2, I'll say that the hardest thing about developing a game in Twine is learning the HTML/JavaScript based language, and getting around some of the oddities of the engine itself.
I'm attempting to build a Life-Sim style game similar to Girl Life/Cursed. So far, the most robust system I've had to piece together is a time-keeping system to keep track of actions spent per time period. Wow.. I haven't even tried to tackle an inventory system yet. Luckily, there are quite a few tutorials for explicit/implicit inventory systems available on Youtube. There is also the great board over at http://twinery.org/questions/questions that can help with some of your questions.
As another poster said.. Having a robust set of tools and variables built in to make it easier for modders to drop things into your game will be a HUGE plus. And probably one of THE hardest things you'll be doing. Modding would have to be done within the Twine program you used to build the game, using whichever story format you use. In most cases, that would be Twine 2, Sugarcube 2.
There is a developer on the TFGamesSite forum that has a modding system in place, but I have ZERO experience with it. The game they've developed is called Perverted Education. Hopefully in the coming weeks, they'll explain the modded scene system.
Hay, fellow game maker, just checked out your game, and it's not bad. Making a game is a ton of work, and the critics can be brutal so good on you for putting yourself out there!
The art: if I'm following correctly you're wife is still pretty new to digital art. I'm not sure what she's using but I got a xp -pen off amazon, and it works great. Somethings that may help her art is to vary her line weight and add more shading to her characters. Around the eyes should be a bit darker, and add some cheek bones. Also some of the character's arms look a bit thin. Try to avoid hard lines on cast shadows, but just a bit of fuzz on the edges. I know it's more work, but instead of moving your character slightly to the right during long periods of dialog, try changing the pose a bit. Have a few different standing poses and facial expressions that you can reuse based on what the character is saying (I'm guilty of doing this too in my own game, but i'm working on it)
For the game play: The games I like is when I feel like I have a say in the direction of the plot. It feels like I'm just clicking through the story. One way to achieve this effect is to give your characters stats and based on the user's interaction that moves those stats left or right (Naughty or nice) another way is repeated action with growing intensity, but that action is not linear to the story, the user has to go out of their way to grow a NPC's stat tree.
I'm by no means an expert (Some have even said it's my games are the worst thing they've ever played), but I enjoy talking about game creation if you ever want to drop me a DM. Good luck, it's a good game, and each game you make gets better. Also you should try advertising on some adult game boards (like F95Zone)