Replacement inside held expression

Generally, you want the Trott-Strzebonski in-place evaluation technique:

f[x_Real]:=x^2;
Hold[{Hold[2.],Hold[3.]}]/.n_Real:>With[{eval = f[n]},eval/;True]

(* Hold[{Hold[4.],Hold[9.]}] *)

It will inject the evaluated r.h.s. into an arbitrarily deep location in the held expression, where the expression was found that matched the rule pattern. This is in contrast with Evaluate, which is only effective on the first level inside Hold (won't work in the example above). Note that you may evaluate some things and not evaluate others:

g[x_] := x^3;
Hold[{Hold[2.], Hold[3.]}] /. n_Real :> With[{eval = f[n]}, g[eval] /; True]

(* Hold[{Hold[g[4.]], Hold[g[9.]]}] *)

The basic idea is to exploit the semantics of rules with local variables shared between the body of With and the condition, but within the context of local rules. The eval variable will be evaluated first (regardless of whether the condition ends up being True - as in this case, or False - thanks to @luyuwuli for pointing out the problem in the original wording for this part) , inside the declaration part of With, while the code inside the Condition , here the body of With (g[eval]), is treated then as normally the r.h.s. of RuleDelayed is. It is important that With is used, since it can inject into unevaluated expressions. Module and Block also have the shared variable semantics, but wouldn't work here: while their declaration part would evaluate, they would not be able to communicate that result to their body that remains unevaluated (more precisely, only the part of the body that is inside Condition will remain unevaluated - see below). The body of With above was not evaluated either, however With injects the evaluated part ( eval here) into it - this is why the g function above remained unevaluated when the rule applied. This can be further illustrated by the following:

Hold[{Hold[2.],Hold[3.]}]/.n_Real:>Module[{eval=f[n]},
   With[{eval = eval},g[eval]/;True]]

(* Hold[{Hold[g[4.]],Hold[g[9.]]}] *)

Note b.t.w. that only the part of code inside With that is inside Condition is considered a part of the "composite rule" and therefore not evaluated. So,

Hold[{Hold[2.],Hold[3.]}]/.n_Real:>Module[{eval = f[n]},
    With[{eval = eval},Print[eval];g[eval]/;True]]

(* print: 4. *)
(* print: 9. *)
(* Hold[{Hold[g[4.]],Hold[g[9.]]}] *)

But

Hold[{Hold[2.],Hold[3.]}]/.n_Real:>Module[{eval = f[n]},
   With[{eval = eval},(Print[eval];g[eval])/;True]]

(* Hold[{Hold[Print[4.];g[4.]],Hold[Print[9.];g[9.]]}] *)

This should further clarify this mechanism.

RuleCondition provides an undocumented, but very convenient, way to make replacements in held expressions. For example, if we want to square the odd integers in a held list:

Hold[{1, 2, 3, 4, 5}] /. n_Integer :> RuleCondition[n^2, OddQ[n]]
(* Hold[{1, 2, 9, 4, 25}] *)

RuleCondition differs from Condition in that the replacement expression is evaluated before it is substituted. The second argument of RuleCondition may be omitted, defaulting to True:

Hold[{2., 3.}] /. n_Real :> RuleCondition[n^2]
(* Hold[{4., 9.}] *)

It is very unfortunate that RuleCondition has remained undocumented for so long, given its extreme usefulness. The Trott-Strzebonski trick discussed in @Leonid's answer is one way to achieve the same result using only documented symbols:

Hold[{2., 3.}] /. n_Real :> With[{eval = n^2}, eval /; True]
(* Hold[{4., 9.}] *)

A slightly less verbose technique uses Block:

Hold[{2., 3.}] /. n_Real :> Block[{}, n^2 /; True]
(* Hold[{4., 9.}] *)

Judicious use of Trace reveals that both of these techniques ultimately resolve to RuleCondition. One must make up one's mind whether it is better to use the undocumented RuleCondition or rely upon implementation artifacts in With and Block. I suspect that the behaviour is unlikely to change in all three cases as so much Mathematica code depends upon the existing behaviour.

Although less magical, it can be done by ReplacePart

expr = Hold[{2, 3, 4, 5}]
pos = Position[expr, _Integer]
newparts = Extract[expr, pos] /. n_Integer :> n^2
ReplacePart[expr, Thread[pos -> newparts]]