About to start DMing a group with just two players. They and I are both quite interested in doing Waterdeep: Dragon Heist.

Two questions:

I have not read all of the seasons cover to cover yet, any that lend themselves better or worse to a small party?

How best to adjust difficulty? I figure I'll need to use multiple techniques... Early on I can have fewer Kenku, and have Renaer join them, but I don't want to have to heavily modify every encounter.

I won't run a DMPC, but I could allow them access basic hireling that keeps their mouth shut (maybe a warforged).

Or have them start at level 2, applying milestone leveling, they end at 6 instead of 5.

Other options?

With two players, it might be easiest to just have them both play two characters; you'd probably need more like +2 levels to make content designed for 4 PCs work out for 2.

I have only played the Xanathar timeline, but I think that they are all equal difficulty level, I could be wrong though.

One method that might work is start the characters at Level 3 rather than level 1... That way they have extra abilities and HP to match the encounters.

Hope this helps!

 In my opinion, Manshoon has the easiest victory conditions, but a 2-player group will have to avoid getting into fights with the Doom Raiders.  Jarlaxle is most prone to letting your guys live to toy with them.  The Cassalanters doesn't have a lot of fighting, but it's a big investigation and two guys might miss important clues.  Xanathar seems likeliest to end in a fight that two 6th level guys can't win.  So I'd look at Jarlaxle or the Cassalanters.

I'd definitely start them at a higher level.  2 players don't have much economy of action.

Careful with the Cassalanters, my players hate nobles, and they burnt down their estate, killing everyone inside, besides themselves and the Black Viper.