Personally the issue is how playable the game is with different character combinations if you get bottlenecked down to a small party that won't change, particularly if your "main" isn't one of the core roles.
What are these core roles in dnd 5e that you can't fill in with wide variety of classes?
While I have no experience actually playing 5E (my gaming group imploded before its release), I have extensive experience with prior editions (where this issue would be unquestionably a major problem for a CRPG and fairly challenging even in PnP) and CRPGs in general. As mentioned earlier in the thread, CRPGs are in general not at all forgiving of a party that can't detect and disable traps or unlock locked containers (it is quite usual for most locks to not have keys that can be found and to punish players who break open the container by destroying some or all of the loot within). Stealth is usually less of an issue, however. CRPGs also usually assume a certain level of access to magical healing, and as a result often include enemies that inflict an array of negative conditions that require magic to remove (or extensive resting) or areas where resting is restricted. I am less concerned about the need for utility spells (many of which are not on the warlock list, for example) or a heavy armored frontline fighter, as what we've seen demonstrated suggests those can be worked around. In PnP any of this can be worked around, but a CRPG has less ability to respond to player creativity than a DM does, and less ability to tailor encounters to the party that actually exists.
Proficiency in thieves' tools is rogue (or the criminal background) specific. This can by dealt with to some extent by multiclassing (though you may be delaying or even foregoing progressions in your main class depending on the level cap), or if they include feats (which I haven't seen specific reference to). Magical healing is more broadly available, but none of the promotional material or interviews I've seen have said with certainty that there are companions other than we've seen, and while it is not unusual to keep a couple secret for spoiler reasons, concealing most of them is no longer common. If you have seen an interview or other official statement where they mention feats or additional available companions, I'd be glad to hear of it.
It is entirely possible I'm jumping at shadows and Larian has set it up so that deciding on a party that contains neither Shadowheart nor Astarion is -not- going to result in a miserable time as you forego most loot, are deprived of xp you were expected to get from disarming all the traps you've been taking on the chin and are therefore underleveled, and have to save scum every combat to make sure you get through with minimal damage because you aren't allowed to take a long rest in an area you can't escape until you've beaten the local boss. There are games where having neither a rogue nor a cleric would be excruciating, and since we've been told we're going to be restricted to a single loadout of 4 party members and have been presented with a small list of companions including only one rogue and one healer, I don't think it unreasonable to at least raise the possibility that this might be a problem. I will be happy to eat crow if I discover otherwise - I don't want there to be problems, I have no objection in principle to the party getting winnowed down for story reasons as was the case for a large chunk of BG2, and provided the story is sufficiently engaging I will probably do multiple play throughs to get the storylines for each NPC.
