I'd say medium map-size, 4-5 AIs, difficulty Tough-Challenging. If you choose all-abundant settings I'd leave research-speed to normal, if you set planets/start to less then it might be a good idea to up the techspeed one tick.

There are some AAR's in the specific setion which describe such things well, you might want to check these.

There are folks that prefer to play shorter games and these folks tend to play ZYW's (zero year wins) and there are very specific strategies along with a couple of different types of settings one would use dependent on which strategy or style one was using.

Another set of people tend to just go for monster scores and then that implies the largest galaxy size along with the maximum number of planets and maximum number of opponents and minors along with the fastest tech rate.

There are also ways to play for a max score while at the same time being able to also submit it as a ZYW although these are by no means quick games.

Then there are countless other ways to play that are highly dependent on the style that you prefer to play as well as your current state of knowledge of the game.

The settings that Maiden mentioned are certainly not unreasonable but you could also come up with dozens of other "reasonable" settings as well. It all depends on what your goals are. I always want to play at the maximum difficulty but Tough can be indeed be pretty tough and the biggest jump is getting from Obscene to Suicidal.

The thing is that there are many tricks and shortcuts however I still believe that anyone that plays Suicidal should be able to win a straight up game against Suicidal opponents by at least being able to equal their rate of colonization and preferably being able to out-colonize the Suicidal AI by a factor of 1½ to 1.

Once you can do this then you can start learning the tricks and shortcuts that allow you to exploit the AI for maximal score. If of course that's what interests you.

I just feel the need to add some minor bits here...

First off...the first two posters to your question are very respected for intimately knowing the game, and Jim has given plenty of great input himself (My apologies if you have many more responses...I have seen a few through scouting and all are very useful/to the point...but let's give it up for Maiden...and Mumble is a Greek among Romans...a compliment in my world...the father of some beautiful ideas).

Second...to repeat statements...it is very much a matter of choice.

-A 'Get the feeling game'

   Small to medium map (Large if especially a fan of immense games)- 2-3/3-5/(5-9) opponents. Mega Events OFF(very personal...but on my first few games the comp generated events that easily turned me from losing to winning, thus killing my hopes of a 'thinking' man's game...of course now long dispelled). 4-5 Minor civs. The real decision is in amount of habitable planets/number of stars. For a good feel, I say common on both and above. This way you deal with a mini-colony rush/exploration period.

   From the sounds of it, you understand 4X games in general, so I recomment at least tough difficulty or better. There may be one or two rough spots of questioning which route to go (personally, I kept feeling that I needed military quicker and quicker...more because of my tendancy to fight early wars in Civ than GalCivII tactics)...but you can overcome many mistakes at tough and still remain competitive with the comp...with a good idea of 4X games...and these mistakes will actually help hammer out your more intensive strategies while still keeping the game in your reach.

  This type of game will take you quite a few attempts in order to fully understand/appreciate the game, but it really encapsulates the best of the AI and the scope of the game...all without AI cheating.

Final bits- Mumble's categorization is a great way to see what path you want to take this game. I am a huge fan of long 4X games with a lot of build-up and history, but have recently become enamored with the prosepect of quick ZYW games while hammering out plans for bigger games.

All personal, but hope it helps

-Scanian

The previous posters pretty much said it all. One comment:

This is indeed very personal, and I think comes down mostly to how much you care about winning/losing. As Mumblefratz's post stated there are many, many ways to play and there are certainly some players (such as myself) who just play for "a story" and don't care a huge amount about the outcome. Mega events can indeed be very destabilizing, in your favor or against it, so depending on how much the outcome matters to you you may or may not want to turn them off.

Edit: For some reason the quote box is all weird...

I myself usually play medium-large galaxies on Tough, 8 AIs for larges, 4-6 on mediums, common stars/planets, extreme planets set to rare. If I want the feel of an epic game I go Gigantic, max AIs, common stars, Tough, and occasional or uncommon planets. All on normal research setting, mega events on, tech victory off, and minor races set to random.

I just put uncommon or occasional cause I hate sending transport after transport to capture planets. Basically all the civs with high soldiering that survive up to this point win. In gigantic galaxies the Drath are almost unconquerable if they have enough planets. Also the settings I outlined for large work with huge as well.

Well I usually don't have this issue as I'm usually the Drath. Having 0% taxes and still making hundreds of BC per year is awsum. But anyways, I had this issue with the Arceans once, they built some of those things that give them soldiering and were a pain in the arse to conquer, even though I was the Drath with all soldiering techs researched. Also I said ALMOST unconquerable, they aren't unconquerable it just takes more time than its worth unless they're the last civ.