I think it comes down to what people think is best, settler colonies, or Portugal Inc. trade only.
If the problem of Portugal is a small population wouldn't it be best to create new population centers where permanent bases can be set up? or is the creation of a colony more expensive than rewarding?
It depends on where is set, its defensability, the economic type of activity in it, etc.
Personally I recommend good settler colonies in good and fertile places, with some trading spots in other regions to control a portion of world trade.
Regarding the settler colonies, there is the issue of choosing it over economic concerns, for example, Portugal was fond of places where Sugar cane could be grown and explored, but in the very long term, its preferable a place that serves for regular agriculture, and that can sustain a large and dense population, without extra health concerns over the climate.
In later stages maybe a bit more of tolerance over the choice of settlers (allowing immigrants from different religious or ethnic beliefs in exchange for loyalty), would help boost the population (a bit more than even the good natural growth the Portuguese people had in those areas of settlement - pus no dispersal in multiple trading posts and countless conflicts in North Africa and the East would increase even more the avaliable population for the colonies).
Another relevant issue is the financial and intellectual capital that can be preserved by not expelling nor confiscating goods from the Jews and Moors living in Portugal (most Jews stayed in Portugal, but the best minds and many fortunes were lost either because they emigrated or the Crown took it) - this would also increase the population a little more over the course of the centuries.