My main character is a Bard 6 / Warlock 4. I pushed Warlock to 4 in order to get the ability improvement feat. If I had for example done Bard 7 / Warlock 3, my charisma would be 2 lower now. I could consider a lot of different options for my main character, but I would always use a character class based on charisma. There are huge advantages in this game to making your main character the "face" of your party, with high charisma and a proficiency in Persuasion, with Deception or Intimidation being an option too. There is a very large number of dialogue options that can be resolved with Persuasion checks, and some of them are rather essential, especially in the interaction of your main character with the companions. You can lose companions or have them develop in ways you don't want if you can't persuade them otherwise. And if you aren't skilled here, you could only either save scum or accept the bad results.

As a multiclass character, my main only has access to level 3 bard spells and level 2 warlock spells. I compensated for that by turning him into a half-illithid and using all the 21 tadpoles I found on him. Reaching Act III unlocked the final level of those illithid powers, and I found it much better to use all the found tadpoles on just one character instead of trying to spread those powers. The final level of powers is really good, and makes up for the lack of high-level spells on my main. Note that for the power of cantrips, it is the overall character level that counts, and so I already have 3 Eldritch Blasts, as BG3 gives the third one out at level 10 already. Very often my main can simply cast Hex on an enemy and destroy him with Eldritch Blasts, which makes him very useful in prolonged engagements, as this doesn't use up any spell slots.

The reason I took bard besides warlock is that I am also using my main character as the one doing all the Sleight of Hand checks. I would very much recommend having one character in the group with high dexterity and a proficiency in Sleight of Hand. There are a huge number of locks to pick and traps to disarm. That character doesn't need to be the main, though. You could use Astarion as a companion for this, or some hireling. In my second playthrough I used my ranger for this, and that worked well too. Although intelligence is a dump stat 8 for my main, I am using the Warped Headband of Intellect from the ogre in Act I to have 17 int, which gives me reasonable success chances for various knowledge checks as well.

My second character is Shadowheart. What is absolutely essential about that is that you should have a character in your group with access to the Guidance cantrip, a cleric or druid. I'm repeating myself here, but Baldur's Gate 3 has you do hundreds of skill checks. Anything you can do to improve your chances of succeeding those checks is good, and thus I would consider access to Guidance essential. Note that if you kill the Strange Ox, you get a ring that adds another 1d4 to your skill checks if you are shapeshifted. And if you have the Deluxe Edition of the game, you have the Mask of the Shapeshifter, and can always have that bonus.

Clerics are rather good in Baldur's Gate 3. And the story of Shadowheart is very much weaved into the main story of the game, especially in Act II. I respec'd Shadowheart to life domain, but kept her as single class cleric, now level 10. Spiritual Weapon at spell level 2, Spirit Guardians at spell level 3, and Guardian of Faith at spell level 4 are things that I use in basically every major combat. And Guiding Bolt is rather good for a spell level 1 option. Another spell level 3 that I used a lot in Act II is Daylight, which not only is extremely helpful against shadows, but also brightens up your screen considerably, and makes it much easier to see stuff in dark places.

My third character is Gale, although I find his personal story somewhat weak. Having a self-destruct button that kills the whole party and ends the game is probably the most useless ability of any character in any RPG ever, even if it technically gets you an "ending". In case you wondered, yes, that gives you an achievement, and 5% of BG3 players have that achievement. All of which then reloaded a previous save and kept playing, I assume. Anyway, having a character with access to arcane spells is rather useful. And a wizard can have access to pretty much every arcane spell in the game, because he can learn them from scrolls. That makes a wizard a lot more versatile than a sorcerer or warlock. Especially since in BG3 you can select different spells anytime outside combat, no rest needed. Which is very useful for ritual spells that last until the next long rest, like Longstrider. Gale is casting that on all of my characters at the start of every day. Spells like Enhance Leap or Featherfall help your group to get around. And arcane casters have the best selection of area of effect spells that go boom, like Fireball. Note that there is a bug / feature in BG3 which allows you to make a multiclass sorcerer X / wizard 1, and still learn all spells from scrolls. I am not sure whether that is working as intended, because that combo is pretty overpowered. In my second playthrough I used a sorc/wiz like that, and twinned Haste on two DPS characters is extremely powerful.

The last of my characters is Karlach. With the magic items I found up to now, I was able to get her to AC 18, which is high for a barbarian. And the damage output when raging is higher than that of Lae'zel as a fighter. Having said that, Karlach's role in the group as melee "tank" is basically interchangeable with any fighter or paladin. I just like her cheery disposition. And with D&D rules not having a lot of ways to hold aggro, I could probably also use for example a ranger as damage dealer. Note that I do switch out Karlach for Lae'zael when the story calls for it, e.g. when visiting the githyanki creche.

Although I never use Astarion or Wyll in combat, sometimes I put them in the group for a social interaction that is related with their backstory. But even if I didn't, I couldn't totally ignore their backstory, because sometimes camp events just pop up that involve them. My error basically was to talk to them and invite them into my camp. I do consider it completely possible to do a first playthrough with Shadowheart, Gale, and Lae'zael as companions without ever picking up Astarion, Wyll, and Karlach. Then you basically wouldn't see their stories, and could do a second playthrough with a "fresh" set of companions.

Personally I have given up on the idea of a second playthrough in 2023. I will finish the game with the group I described in this post, and then at the very least have a long break. There are a number of reasons for that, but the most important one for me was discovering that you can't really do an evil playthrough and play a very different story from the good playthrough. By the end of Act II you know who the bad guys are, and not fighting them is not an option. You can fight them with the purpose of usurping their evil powers, sure, but you'd still fight them, not join them. The second reason is that Baldur's Gate 3 has a lot of non-combat content, in the form of dialogue and exploration, and a second playthrough would have you go through much of the same dialogue and find the same items in the same crates. So I would like to forget a lot of that before going through this again. And the third reason is that Act II is less polished than Act I, and I hear that Act III is even less polished. Given Larian's track record, it is very likely that one day I'll get a free upgrade to a "definitive edition" of Baldur's Gate 3, in which Acts II and III are improved to the same level as Act I. And that would probably be a better time for a second playthrough, rather than just after the first. It isn't as if 2023 is short on great games.