Technology wise? (Eg: I've seen it said that medieval stonework was much better.)
Structure wise? (Eg: It feels like that there were more republics in Antiquity, although I may be wrong, and the Feudal System seems to have been a Medieval invention.)
Otherwise? (Feel free to chime in.)
Answers to any or all of the above welcome.
Both "Antiquity" and "Medieval" eras encompass huge geographies and vast spans of time. This makes it very difficult to generalize about major differences.
If you could limit the scope (for example: major differences between the Roman Imperial period from 43 BC to 480 AD and the early Medieval Period from 500 AD to 1100 AD in Western Europe) you would have a better chance of being able to define major differences. (Though even this scope is still very broad).
The other challenge would be how to cope with major changes which spanned both periods (such as the rising influence of the Christian Church, or the increasing insecurity and exposure to invasions, raids, and violence).