Depends if you hold your breath

The player's handbook p.183 gives rules for suffocating. In brief a creature holding its breath can last for minutes but a creature that runs out of breath or is choking lasts a number of rounds equal to their constitution modifier before dropping to 0 hp.

The question then is whether a PC is holding their breath when being suffocated by, say, a darkmantle. The darkmantle monster entry says a creature engulfed is, "unable to breath", but gives us no further information. This seems to be up to the DM to rule if a given character was able to begin holding their breath, and so lasts minutes, or if the suffocation begins suddenly and they can only last a few rounds.

Personally I'd go with effects such as this happening too suddenly to hold your breath since it keeps the effects relevant in an average battle.

RAW, you can hold your breath because Jeremy Crawford says so

If we're counting JC tweets as RAW than all that matters is JC says you can. As you explained in your question this means that the suffocation part of fighting a darkmantle is unlikely to ever come up in a normal battle, and I'd say this takes away what makes the darkmantle an interesting monster. Just another strange part of 5e RAW.

Theoretically Yes, but only works for negative con mod

Though it doesn't explicitly state it I would consider "engulfed by water" to be equivalent to being underwater. Thus triggering the suffocating rules.

Suffocating: A creature can hold its breath for a number of minutes equal to 1 + its Constitution modifier (minimum of 30 seconds).

However for most creatures the duration of watery sphere won't be enough to cause them to drown, even if they fail every saving through. Due to the duration of the spell.

Watery Sphere: Duration: 1 minute

Constitution below 10

Even for a creature with a negative constitution they would have to fail a minimum of 6 consecutive rolls before drowning. Assuming they have the worst stats in the world they will still succeed at least 30% of the time. (Probability of a Natural 20 from 6 attempts). Technically a natural 20 is not an auto-success on saving-throws but most tables I have played at accept it as a house-rule. So if you have a high saved DC (>20) or the target has a negative modifier in strength you may have a chance to succeed.

Constitution of 10 or above

Any creature with a constitution of 10 or above will never suffocate as they can hold their breath for longer than the spells duration. Though forcing them to hold their breathe can prevent them from casting spells or communicating which is fun.

Interaction with Hold Person

You mention that the combination of Hold Person and watery sphere could be quite strong. This would come from the effect of hold person.

Hold Person: ... The target must succeed on a Wisdom saving throw or be paralyzed for the duration. ...

The paralysed condition states

Paralyzed: The creature automatically fails Strength and Dexterity saving throws. Attack rolls against the creature have advantage.

This would mean casting Watery Sphere on a target already held by Hold Person would automatically succeed. The extra save does increase your chances of the target reaching 7 rounds without saving. However, the chance of a creature having negative modifiers for Strength, Constitution and Wisdom is extremely low and it is likely that they will easily succeed at least one of these saves.