Eh, I wouldn't say it's safe to say at all, Bayonetta 3 seems like a sure thing for E3 2018 and 2019 too but was a no show, and BOTW1 seemed like a sure thing for E3 2015 before they announced at the 11th hour that it wouldn't be there despite being revealed the previous year's show.

BotW2 update and holiday release date.
Probably some Splatoon 3 footage.
More video of the two pokemon games.
Hopefully something...anything(!!) Metroid. Don't expect Prime 4 but hopefully a Prime Trilogy announcement or 2D Metroid announcement.
Hopefully some sort of Zelda collection.
Maybe an early teaser for the next 2D Mario game.
Perhaps they'll officially announce the new Switch model.

Though I guess the only "reveals" in that list would be 2D Mario and Metroid.

Probably also a smaller game or two.

I hope they show us something like a "Switch Pro" I mean an upgrade or a revision, something better than the Switch Lite. I think they will mostly share información about known and announced games, and maybe 2 or 3 new games

It was confirmed by Kamiya that "It's safe to expect news this year" regarding Bayonetta 3. That could mean TGA 2021 for all we know, but at that point it will have been 4 years in development. I don't think Bayonetta 3 needs more time in the oven before showing us a trailer considering Kamiya has consistently said development has been going very well. 

https://www.ign.com/articles/bayonetta-3-hideki-kamiya-says-its-safe-to-expect-news-this-year

BotW1 not appearing at 2015 E3 was an entirely different situation and not indicative of them showing off BotW2 this year or not. BotW1, in case you aren't aware, was going to be released on the Wii U originally. As the Wii U failed and the scope of the game got bigger, it's likely that Nintendo thought very early on that they needed to delay it and release it on their next system. We do not know if internally they wanted the Switch out holiday 2016--which could have been the case. So it's entirely speculation. But as I said before, BotW1 not showing up at E3 2015 is not evidence in any form that they won't show BotW2 this year. In fact, you could argue that because they didn't show it last year, they will show it this year. (Considering the E3 of 2016 they hounded us with information on Botw) and 2020 was the year they revealed nothing on BotW2. 

E3 2014 BotW reveal

E3 2015 no info

E3 2016 hound of info

E3 2019 BotW2 reveal

E3 2020 (or lack of E3) no info at all

E3 2021 BotW 2 hound of info? - it's safer to bet on this speculation then "well they didn't do BotW1 info at E3 2015"

Smash character reveal, those are always eagerly anticipated.

Considering Sony's recent openness, Ratchet and Clank are coming to Smash! How's that for a prediction?

Kamiya's a troll, I wouldn't take anything he says regarding new game news as reliable. His "next week in gaming magazines" line has become infamous for example.

Regarding BOTW2, I'm still not expecting it to be at E3; it's not impossible, but I'm feeling like 60% chance it won't be there, 40% chance it will. Nintendo love to hold out on games they know fans desperately want to see. I kinda expect them to properly reveal BOTW2 when they reveal Switch Pro, which I don't think will be at E3.

I think a port of Xenoblade X is not just wishful thinking, maybe it does end up happening, but I think the first showing of one of Monolith Soft's brand new games is more likely. It's already been almost 3 and a half years since the release of Xenoblade 2, I think it's good time to show what they got under their sleeves.

Not sure beyond that, but Metroid, either Prime 4 or 2D, BotW 2, Bayo 3 and Kart 9 seem very improbable. On the other hand, they're absolutely going to show more Splatoon 3 and the Pokémon games footage. It's weird, but it doesn't seem like they could show a lot, it's open for a lot of surprises.