While this wouldn’t include prokaryotic or external organelles, endosymbiosis could produce some of the same desired effects, allowing you to optimize small cells in order to make them better.
In addition, in this thread, one of the ideas was to have a flow chart similar to this, except only for proteins and not for other organelles. Organelle upgrades also exist now, so those could make up the difference, all together giving the player the most options, while also having all the options be interesting and viable.