Well, everybody on this forum should know by now that I don't like Leon, but I think it wouldn't make a difference to me in the longer term if it was someone else, especially in a series like Resident Evil. If it was Tomb Raider for example, with Lara Croft as the one and only protagonist by default, it would be a different case. But Resident Evil, Silent Hill and some other games as well are known for their variation of characters and I think we would quickly grow tired of whoever they chose to bring on too often.
(So... sorry Chris, but if you want my undivided attention, you should consider awaiting me on my bed in nothing but underpants instead of appearing in every single episode of our RE TV series for no apparent reason.)
Talking about reasons: It would be rather difficult to pull through anyway. Imagine Leon on the Ecliptic Express (even though he isn't even with the RPD by this time), Claire in the Spencer Mansion (and still coming to look for her "long-lost" brother only two months later), Chris helping Jill to escape Raccoon City (despite his absence being the reason for all the women in this game going crazy at that point), Jill in El Pueblo (although she has no business with the organisation Leon works for or Ashley altogether), Rebecca on Rockfort Island (though it would make sense to bring on Ada and have her and Wesker compete for Alexia's attention), etc. How could one character's omnipresence ever be explained without considerably altering the canon? The only halfway acceptable compromise would be an entirely new protagonist, but I'm sure we all agree that we don't need another Alice in our favourite series.