Well we do have answers to many of these questions already. For instance the longest ISS stay is 437 days, contrasted against the ~100 days to get to Mars. And the ISS is a claustrophobic cave contrasted against the Starship. The ISS is made of various modules. The zvezda/"star" module is a major support and living module, with a total habitable volume of 47m^3. Starship has 1000m^3 (which is equal to the volume of the
entire ISS). Of course lots of that will be used for supplies, but the nature of the planned missions (multiple ships, supplies/fuel/etc distributed among other ships in the fleet) means a very sizable chunk of it will be available for habitation.
There's also a lot of misconceptions about things like radiation. In general short extremely high energy bursts of solar weather can be quite dangerous. But it turns out that the Starship will already have a rather large volume of appropriate shielding - water! That shield can be used on an as-needed basis because you can see these events coming from far away (yet again, advantages the earlier colonists would not have had).
The ambient radiation is much less of a concern. The worst case scenario is you end up shaving some years off your average life expectancy with a higher overall chance of cancer, but there are some super interesting studies in places like Ramsar, Iran [1]. Ramsar is the most naturally radiated habitated location on Earth, with orders of magnitude higher radiation levels than generally recommended as safe. According to contemporary radiation-cancer models, increased cancer rates should be trivially detectable. Instead they actually seem to be showing a slightly reduced rate of cancer, which some have posited may be attributable to radio-adaptive effects in play! Presumably this would not be true of the first generation(s), but it suggests some extremely exciting generational possibilities.
Basically I would say here that anything a small mission can do, a larger one could do - more safely, more reliably, more efficienctly, with more data, and just generally better chances of success. The costs when you do fail will be higher, but the chances of failure will be lower, and the overall rate of progress will be dramatically higher.
[1] - https://en.wikipedia.org/wiki/Ramsar,_Iran#Radioactivity