was in both last month!
It's completely up to you - there are organised tours going to murano and burano or you can just get the normal vaperetto (water bus) there which is going to be much cheaper. It's very easy to navigate, just go to one of the main drop off points (by the piazza de. roma or the train station) and they've got big electronic signs out telling you which number/letter route to take. If you buy a 24/48hr ticket (recommended) then all routes are included. You can book yourself to watch a demonstration of the glass making at murano https://www.visitmuranoglassfactory.com/ - it's very short but also only 5 euros so worth doing!
I'd recommend taking a walking tour around venice to try and get your bearings a bit and hear some interesting history, but also just be prepared to wander round and get lost. Google maps works okay there, so download it just in case but as long as you can find your way back to the main waterway you'll be fine. Go to Libreria Acqua Alta - flooded bookstore.
In terms of Rome yes it is much bigger. I've been a few times so tried to do a few slightly different things the most recent visit but if you're only there for 3 days I would do the big things like the colosseum, trevi fountain etc - they're famous for a reason!
Again there are absolutely loads of different colosseum tours you could go on - just google - but if you just wanted to go yourself the official site is here warning it is incredibly slow to load. You can choose between just wandering around yourself or a guided tour (I'd do the second). A ticket to the colosseum also covers the forum which is right next door. Honestly you could spend most of a day just in those two places. You absolutely need to book before going or you'll be in a huge queue, if there are even any tickets left.
There are the normal pink bus/red bus sightseeing tours in rome that are in every major city - tbh they all seem to go to the same spots so I'd just go for the cheapest. I think they're cheaper if you book online but can do so on the day. I wouldn't book it for the same day you do the colosseum because its usually a 24 hr ticket - or maybe get it for the evening so you can do a bit one day and a bit the next but also spend some time at the first and last site.
I haven't been on one but a few people have recommended some food/wine tours. Other than that it depends what you like to see - more interested in the roman stuff, medieval stuff, religious stuff, museums, cats, shopping, art????
Oh and the one thing to bear in mind is that there are very very few public toilets in either venice or rome, and the ones that are there you usually have to pay for - usually 1euro50. Even in places like mcdonalds you have to scan your receipt, and there's usually only like 1 or 2 cubicles in a really busy restaurant. It will be very hot and busy so I'd factor in lots of coffee/aperol spritzer breaks and use the loo then.