The nested replace is fine, but as the nesting level increases the readability of your code goes down. If I had a large number of characters to replace I would opt for something cleaner like the below table driven approach.
declare @Category varchar(25)
set @Category = 'ABC & DEF/GHI, LMN OP'
-- nested replace
select replace(replace(replace(replace(@Category, ' & ', '-'), '/', '-'), ', ', '-'), ' ', '-') as Department
-- table driven
declare @t table (ReplaceThis varchar(10), WithThis varchar(10))
insert into @t
values (' & ', '-'),
('/', '-'),
(', ', '-'),
(' ', '-')
select @Category = replace(@Category, ReplaceThis, isnull(WithThis, ''))
from @t
where charindex(ReplaceThis, @Category) > 0;
select @Category [Department]
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