Sorry I found this gem so late in the development cycle, but please spend a few minutes to consider this idea of a during-the-game difficulty slider--now, rather than dismissing the idea offhand, let it bounce around in your head long enough for the incredibly flexible gameplay opportunities to become clear.  (Relatively easy to implement for near infinite customizability!)

Since the early 90s, I've been struck by the inflexibility of 4x games that like to hang their hat on "sandbox."  A player can change flavors and maps and other settings, but usually once a game difficulty is set, much of the gameplay's dynamic is preset, its vast flexible framework...stymied by a setting that won't budge during the game.  (And let's face it: how the AI reacts to the player is one of the greatest appeals.  And no, I'm not advocating behind-the-scenes dynamic changes--that would be prohibitively difficult to properly implement.)

AI difficulty is mostly about scaling bonuses and decision-making processes, correct?  So the program shouldn't care when it applies these calculations--be they unchanging throughout the game or tuned during the initial jostling phase, or even tweaked during the late-game push.  In general, 4x genre difficulty is either too artificially constrictive or too easy/passive, especially when compared to complex gameplay that changes dramatically over its course.  So why have static difficulty in a game where everything else is building/changing?  Why try to pre-balance when it can be done on the fly under the player's control (if the player so chooses, though of course multiplayer would need a locking feature)?

Please bear with me while I give a slightly foggy example of Civ4: I loved that great balance of civ-building and competition, yet I was either annoyed by the untiring, in-my-face, early-game AI on Emperor+ level, or bored by the sluggish "just kill me" performance of the AI on King or lower levels during the late game.  Since I couldn't set the early game difficulty at Prince and the late game at Emperor+, I adapted by tailoring maps/gameplay settings to give myself early game advantages and decent elbow room.  When those super-boosted AIs came for me, I was ready to face them even though I'd had the time to enjoy the early game exploration/building.

Or a more site-appropriate example would be the ability to tone down the early Sophon posturing in harder Endless Space 2 difficulties while keeping them from becoming the galactic whipping boy in the later game.  The AI in ES2 just isn't a match for the otherwise elegant and complex 4x game, and I spent many hours looking for settings that would be a better fit without resorting to the kind of hyper-optimization gaming of mechanics that some would deem cheese.

In any case, all of this trial-and-error fuss could have been elegantly solved with an on-the-fly (or by-the-era) difficulty adjustment that could--as only one example--keep the AIs near my resource level until I could see my synergies were outstripping theirs.  And then rather than let the snowball happen, I could have increased their advantages and aggression to completely rejuvenate an endgame that would otherwise just be rote.  For a single player game, giving this fine-tuning power to the player is another great leap in their ability to customize and enjoy their game.

From what I can observe as an avid gamer, most of the difficulty changes come from applied multipliers for the AI (which can be stupidly unbalancing in one part of the game yet fairly compensating in a different stage), and the AI decision-making process (usually based around how fast it builds toward end goals as well as its aggression).  Could these not be codified/controlled with a slider, dramatically changing the game feel/progression just by when and how that difficulty adjustment is applied?  Since 4x games already track every performance metric, it'd be a simple way for a player to check and readjust.  Or even have an (easily disabled like any other tutorial/advisor setting) in-game adviser make recommendations when it sees players lagging behind or trouncing their opponents.

Imagine all the scenarios/possibilities and the ability to boast true customizability...

Actually, I really really like this idea. I feel like if it became a regular feature in 4Xs it could help reduce a lot of the tedium players can feel at different points of the game. Not sure how hard it would be to code in and therefore I’m not sure if it’s too late to add, but it’s a definite +1 from me and I hope they can still find time to consider it.