something dumb like make Mr. House the good guy

Definitely not lol. Also it takes place in 2296 so 15 years after New Vegas. Also if they put Benny in it would be pretty fucked up because Matthew Perry who is the only acceptable casting choice for him (did the original VA for the character) is dead.

As for how much is changed, well a lot can happen in 15 years and in the show that includes a few major events that sort of nullify any possible canon New Vegas ending. Caesar is dead, the Brotherhood is still fractured (or split again as fascists often do) and if anything it seems like as I said the Enclave sort of came in and wiped out whatever faction took over the strip. House is possibly still alive but even that is still up in the air as his life support pod is never actually shown. The only postwar House you get is at the terminal where you meet him for the first time in New Vegas. I think they did a good job walking the multi-ending tightrope of New Vegas. Most notably absent is the Institute which again doesn't mean a whole lot since Fallout 4 happens on the other side of the continent.

I imagine they might get teased or be in the background of season 3 and become the major reveal for ending of S3 and story of S4. I know a 3rd season is already planned and I assume it could run a couple more seasons past that without running out of material to draw from if not more. I doubt we will see anything like Big MT in S3 since the show is seemingly setting its sites on Colorado for the next season and BIG MT is supposedly somewhere around southern Nevada/New Mexico (interestingly its speculated that it is in roughly the same geographical location of Black Mesa in the HL series). As for what is known to be in Colorado are both the Legion and the Presidential vault which will likely make an appearance given that they are setting the stage for the re-emergence of the Enclave.