I rented the game. I'm only going to play each campaign once on the normal difficulty. Does it matter who you pick to play as? Without spoilers, which characters overall are better to play as? Are some easier then others? Some have better content? Any opinions appreciated. Thanks!
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IMO, the best is the namesake of the campaign, as its focused on them. They've done a pretty good job of fleshing out the characters though, so it's worth it to play as the "sidekicks" also to flesh out their stories more.
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In my opinion, I think you should play as these characters:
Leon for Leon's story; Helena does play a part but I felt like Leon because of the previous games, so go with him if you want.
Piers for Chris' story; I believe that Piers is the best choice because you hear some interesting lines from Chris' you wouldn't if you chose Chris, and trust me, just play as Piers.
If you're familiar with RE2 - Sherry for Jakes story; it feels a lot more like a story and sequel for her to me than Jake... Like it's her big return to the series. You can still play as Jake, not much is different - I prefer Sherry though, that's personal choice.
Either way, you mind as well go through as another character anyway when you've finished to get the Professional trophy. So up to you.
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It depends if you're more concerned about tactics or story.
Helena has a unique shotgun, which is more useful than Leon's unique survival knife and dual handguns. However, Leon is arguably cooler. There's little difference in the gameplay otherwise for their campaign.
Piers is a sniper, and thus gets a unique rifle (anti-materiel rifle), which is far more handy than Chris's handgun and combat knife. However, Chris is more of a jack-of-all-trades and is better suited for close combat. Choose whichever style you prefer. There are quite a few differences between the gameplay and locations with these two. In terms of story, it's probably more rewarding to play as Piers.
Jake is best suited to hand-to-hand combat, but it has a steep learning curve. Sherry has a stun rod, which is also not particularly useful. The major differences with these two are in the locations; Sherry arguably has an easier time, save for the beginning of chapter 3.