It really depends on the country. You're likely to get by with large notes in Germany without much problem, for instance, but that doesn't mean you'll be able to do so in other countries. (It's said that the Germans were quite insistent on the Euro having €100, €200 and €500 notes, as they had previously enjoyed high denomination Mark notes.)
In the UK, you'll often struggle to spend a £50 note in most shops or bars. £100 notes (which are only issued by the Scottish and Northern Irish banks) are often even more problematic, as most people simply aren't familiar with them so aren't willing to accept them in case they may be forgeries.