easy
Interrupts are easy enough to implement in a videogame: While I'm holding this button down, and the enemy attacks me, do this in return. If we're talking about a real-time game I agree that AEDU (with the "daily" part), doesn't work at all, they'd have to use different timeouts to represent that.
If certain powers have tricky triggers, ignore them. Or simplify the trigger to make selecting it by the gamer in the UI to make sense visually.
A 4e game could have, say, a daily with a 15 minute realtime timeout and an encounter like a 30 second one. So in a videogame you'd definitely be much better off optimizing your at-wills meaning of course twin-strike is even more powerful than it is. But those are balance issues that can be fixed by varying the timeouts or the damage or just errataing the powers themselves. You could still even print out your character sheet in the same format.
4e is definitely way more streamlined. Prone? Easy to implement. Major image spell in 3e / PF? Not so much. 4e grid-based fireball? Easy as pie. Volumetric D&D fireball that expands to fit its total volume in any direction, cracks, shape of corridors? MUCH harder. You need fluid dynamics and air equations -- i.e. real physics -- to make that work.
Some of the AI problems are intractable, hard problems, that would be in any edition, but combat powers would be MUCH easier to optimize the AI around in 4e than in, say, pathfinder. You build neural nets or heuristic probability tables with a few base heuristics input by the designers, and let some genetic algorithm optimize the decision tree. Again, much easier to do that, with tons of powers that are all fairly uniform, than with spells or class abilities that are quite different or built on a non-specific description of what it can do.
I'm not saying all PP features or class features in 4e would be easy, but most are pretty simple and the desired behavior or classes like the warlock, which a lot of smart human players might not even play optimally would pass the muster.
Try coding the insight that a wizard PC might use Shrink on a sword so they can pass it through the gate to his friend on the other side in an AI. This type of versatile, dynamic AI is waaaaaaaay harder in other editions, because spells can have out of combat uses on the terrain that affect, in a roundabout way, the terrain. Trust me, I make RPGs for a living as a gameplay programmer and have 15 titles to my credit. I know whereof I speak. I like 4e for this reason, and am VERY disappointed nobody built a decent subset of it into a game so I can play my dragonborn ranger/paladin when my DM is busy or the campaign fizzles. We only ever got to 13th level in 4e, and everyone in my rather larger circle of gaming friends has since stopped playing. Sad, but true. A 4e game would have allowed me to keep playing it. I like video games, that's not a slight to 4e, but their similarities are well known and NOT bull dung.
I'd rather have to try implementing the 4e PHB than any other edition, for sure. It might not work as well as some other custom ruleset, but you never specified if it's for a real-time game or a strategy game. A turn based RPG on a grid is one of the simplest things you can do, no matter the number of permutations involved in power selection or targetting. Who says the golins always have to behave optimally all the time? Let them make mistakes. You can patch or tweak that, post launch if you have to, once you've recovered the usage/kill metrics and heat maps that you need to mine that type of data.
I would definitely start by hardcoding the tricks from the char op boards, e.g. every ranger, no matter the build, has Twin Strike as one of their at-wills. And so on. I look at my 4e character sheet and see a set of easy instructions on how to run this character on a grid in a turn-based combat. I look at my PF alchemist sheet and see next to nothing (I rarely look at it, in fact) that tells me what my options are for next battle or next round. Sure I keep track of the number of times I've turned into a werewolf or extracts I've consumed and my HP, but aside from that, the exact beast I turn into, the alter self I do that gives me a number of movement -- even breathing and senses -- modulates how I would even BEGIN to think about implementing it in a fun way.
