The Mass Relays were just an iconic thing of Mass Effect for me, as well as others I know. To have a Mass Effect game without them is just going to feel like something is missing. It'd be like watching a Star Wars film without the Force: sure you can do it and it can even be great, but there is something missing.
Plus I still think that the Reapers having been to Andromeda in the past would be able to deal with a lot of issues, and could have lead to good scenes especially if they are the reason for going to Andromeda.
I agree with the Relays being iconic and the sentiment around that.
I would not like it if the Reapers had been to Andromeda, though; especially if they'd built Relays and some "infrastructure". Their programming/purpose was very much centered on preserving life in the Milky Way. They had no need to go to Andromeda and setup shop. Plus, I'd like to be rid of them. They were a great foe, for all their issues that people here love to complain about; but I'm ready for something totally new. No Reapers. No Shepard. I want enough of the species, technologies and cultures we knew to make it absolutely Mass Effect, and then we can start meeting new species and threats.
In practice, it probably won't make much difference that we're now using FTL all of the time, instead of often using Relays. Still, I'm interested in seeing how it works. If it's seamless, without loading screens, I think it could be pretty cool. We'll still have all of our other familiar tech, as well, so I think it will still feel like home, so to speak.