What do you do to keep subsequent runs interesting?

Besides changing the Pokemon you use, is there anything you do to keep subsequent runs of a Pokemon game after your first interesting? Nuzlockes? Other challenges?

I do challenges. Nuzlockes, Wonderlockes, Solo Runs, Mono Type Runs, all that good stuff. I also do unofficial challenges like only using the Pokemon on the first route.

As time goes on, I tend to use more strict self imposed rules. I dislike Nuzlocke and a lot of other standard challenges, so I came up with my own ruleset that makes the games a lot harder.

a) The game must be played on the "set" battle mode. Not only does it make the battles more like online multiplayer, but you save a TON of time not being asked if you want to switch all the time.

b) Hold items are okay during battles, but the use of healing, stat boosting, and other "man made" items like Potions, revives and X Defends are ALL banned during battles. It's okay to use them outside of battles, but during fights is forbidden. It makes it more like online multiplayer, and the fact that certain opponents still use them adds to the challenge.

Other rules tend to be game specific, but the biggest one is to turn exp share off in gen 6 and 7, and no Pokemon Amie or Pokemon Refresh boosts.

Try out these rules, and you'll probably see these games in a new light. It certainly makes you have to think more strategically, and you'll actually want to teach your Pokemon healing moves for tough battles. I've never gone back to the old ways once I started doing this.

I've tried a couple of the challenge variations which are quite fun. Nuzlockes and Wedlockes are good to try out, they actually change up the gameplay in more ways than you'd think making it much more enjoyable than a standard run.

I don't really do many challenges but I usually tend to ban myself from using a similar team composition and try out types that I don't normally afford a spot on my team.

I typically just do small things to increase the difficulty for myself, like monotype runs, and like Peko was saying, having the battle mote on "set", and I basically always have the exp. share off (I just hate grinding so *if* I have to I'll use it then). Coming up with more rules could be fun though, like taking away the use of healing items during battle. I'd also like to try doing a playthrough with a friend.

When I used to pretty much know my way through Emerald like the back of my hand I used to do all sorts like use "Set", try to solo run it with Blaziken (given how many Tentacool / Tentacruel you encounter on the water and both Drake and Wallace resisting both of its' STAB typings this is tougher than it sounds), but as I play less frequently now I tend not to have to do as much (I had to get on Bulbapedia's Walkthrough on Emerald to remember where to find some of the Water-types this last time i played).

As well as changing my team up I often decide to just be ridiculously fussy about things, for example only using Pok? Balls and whatever balls where introduced in that generation (so in HgSs I only use Pok? Balls and Apricorn Balls, whilst in Diamond / Platinum I use Quick and Dusk Balls mainly due to not liking Heal Balls' design), then insisting on getting a particular nature, and even in my last Emerald game actually comitting to capturing a Feebas then maxxing out its Beauty stat and evolving it. In this case it involved getting to Mossdeep City first, then earning enough money for Dive Balls, then finding the Feebas tile, then capturing as many as possible in order to get the Bold nature I wanted and decent IVs, and then not being able to evolve it until post-E4 when the Blend Master finally turned up.

My last two Gen IV games due to having 2 DS I've used Egg moves, so that not only am I using a different pok?mon to normal but it has a set strategy that may not always come off - Curse Munchlax in Platinum was a beast, but my Quick Feet Ursaring with Toxic Orb, despite being lv. 45, still didn't beat a single Johto Elite Four opponent for speed and struggled to take hits.

Going back to the generation-pok? balls restrictions, I tend to also force myself to only use pok?mon introduced in that generation (I made an exception for a Flareon in Platinum as I'd never used one and this one was migrated from Kanto with Body Slam for that attack stat, and Black 2 forced my hand a bit as it was soon going to turn into a solo run otherwise), and items from that generation (bar the Toxic Orb none of the team that just beat Lance had a post-Gen II item). i've thought about even doing moves - whether only doing moves that were available in that generation (thus making LeafGreen and HeartGold far more tricky than all my other games), or only moves introduced in that generation, which I think might just be insane even for me.

I used to do Nuzlockes and similar challenges quite a bit too keep things fresh and exciting. Nowadays, I merely just use a completely different team on the game that I played longest ago, which still makes playthroughs really fun.