Blade 4 is a topic Wesley Snipes has spoken on and is willing to move forward with given the right script. Marvel might however go with a reboot of the Blade franchise rather than a fourth installment of Blade depending on finalizing contractual issues with Avengers cast members.
Seeing Wesley Snipes reprise his role as Blade in Blade 4 if it were to move forward would sound great, but
not many share the same opinion. I have heard rumors of a nice method that can be taken into play at how this can be done, if not Blade 4 then a Spider-man cameo appearance would play a nice role into rebooting the Blade franchise, and in-time add him to the Avengers saga. I also heard some rumors about some people requesting him as Black Panther, although the idea is good, he wouldn't fit the part as Panther is younger, seeing Black Panther on the Avengers sounds good as well. The way Blade usually makes smartass comments, it would be great to see him interact with Tony Stark lol. I can see some very good comedy being added to the Avengers. The way Spider-man was remade, there were improvements, I can see either a fourth Blade installment or reboot then moving forward into the Avengers initiative. Kris Kristofferson reprising his role as whistler would be great to see if Marvel were to stick with Blade 4.
For this decade, Christopher Nolan has proven to be a very talented Director for the film industry, he has realistic visions for his films as well as being creative when bringing the comic story line to life. Someone with similar creativity would most definitely be able to either continue the Blade saga with a fourth Blade installment or reboot the franchise depending on which direction Marvel wants the character to take. Wesley Snipes has already said he would be up for a fourth Blade installment, if the story line is done right. Wesley Snipes' work speaks for itself.
Can he be replaced? sure, with someone as good as him? possibly, if Marvel could find the right talent. There would only be one problem with replacing him, replacing Snipes as Blade would be like replacing Hugh Jackman as Wolverine.