There are no real downsides. However, few people create tilesets at all nowadays, and more tiles means more time spent in development, so huge tilesets remain uncommon for now.
Scripting makes it possible to use multiple tilesets in a single level and change their palette on the run. As a result, in pursuit of originality and enticing visuals, it's becoming very common to mix and match tilesets, modify their color schemes, introduce new elements, etc. Sometimes people will load Jungle background into a Carrotus level, other times darken foreground tiles and place them in the background. I'm inclined to say those are things for level designers to worry about, not tileset artists.

Single player hasn't been the most popular game mode to create levels for recently, with multiplayer uploads being much more common, but it's still around, and episodes do occasionally happen - such as Holiday Hare '17, uploaded just a month ago by community effort.

AngelScript is very commonplace, but by no means a requirement. It's most often used for small gameplay modifications and cosmetic touch-ups, and rather rarely utilized to its full potential. Personally I don't think there's anything useful for scripting that you could include in a tileset. A tileset should contain tiles, and for all visuals that have no business being used as tiles, custom sprite sets (j2a files) are a better fit.

This, in fact, has some potential consequences in tileset design. Some original and interesting solutions from the past could be considered suboptimal nowadays. For example, if you recall the keys and fireballs in Agama's Heaven, or some chess piece enemies from Kejero's Tomb Rabbit 2, things like those would nowadays be much better accomplished by sprites and scripts. Keys could be actual pickups and give you points, fireballs could be actual projectiles and explode upon impact, whereas chess pieces could be actual enemies and be damaged by bullets. If you have original ideas along those lines that perhaps aren't quite fit for being tiles, consider attaching a dedicated sprite set to your tileset instead. If you don't write scripts yourself, you shouldn't have any trouble finding someone to either help you or do it for you, e.g. in the thread made specifically for that purpose.
That about sums it up. Much like I said, any scripted features are usually the responsibility of the level designer, not tileset artist. Although, I would like to say tiles dedicated to indicating instant death pits are always welcome. It can be as subtle as some cave tiles fading to pitch black towards the bottom, or far more literal like some imagery involving skulls and crossbones, as long as the message becomes clear after at most one fall. It's something I commonly find missing.
Scripting also enables inserting more layers into a level. This means that your tileset may reasonably have more than the usual 2 or 3 dedicated background layers, as well as that no one will get mad if it doesn't have a separate cave version of every masked tile (although some people, such as those who prefer JCS over MLLE, may still find it preferable).

The maximum resolution supported by JJ2+ is 800x600, compared to the previous 640x480. Many tileset backgrounds don't utilize vertical space very well and cover only a small fraction of that space. Foregrounds often include small visual details that are not very significant. That's not ideal. Try to think big.

JJ2+ introduces 3 new tile types: invisible, heat effect, and frozen. It may be worth experimenting with them to see if you can utilize them in any way. It also introduces 3 new textured background modes, and background fade position may be modified.

Using scripting, water may be moved to different layers or made invisible, and its color may be modified. It's possible to enable lighting effects even when water is active.

AngelScript has a feature known as layer sprite modes. It's quite inefficient and as a result its uses are niche, but it's also reasonably possible to experiment with.


Hopefully, this was an extensive but not overwhelming answer. Think of scripting and JJ2+ features as means to achieve more freedom, not enforce more requirements. Much like I said, we haven't had many new tilesets recently, and we deal with what we have just fine, attempting to give them fresh looks thanks to AngelScript, so you don't have to necessarily do anything differently. We'll welcome any new tileset with open hands.